INTRODUCTION ____________________________________________________________________________________________

1.1 INTRODUCTION

The growth in understanding the coordination chemistry has been greatly

stimulated by the developments in catalysis and understanding its role in

biochemistry. The key components of coordination compounds are metals, ligands

and metal-ligands interactions. The concept of a metal complex originated in the work

of Alfred Werner1, the father of coordination chemistry who in 1913 was awarded the

first Noble Prize in inorganic chemistry. A description of his life and the influence of

his work played a vital role in the development of coordination chemistry. The

chemistry of Schiff’s base complexes continues to attract many researchers because of

its wide applications in analytical chemistry, catalysis, food industry2, dye industry3,

fungicidal4 and agro chemical activity5. Schiff’s bases are an important class of

ligands in coordination chemistry and have many applications in various fields6. In

chemical science the chelating characterization of Schiff’s base transition metal

complexes containing different donor atoms such as nitrogen, oxygen and sulphur

exhibit enhanced applications in the advanced chemical fields like anti-HIV,

fungicide, antiviral, insecticide, anthelmintic, antipruritic, anticancer, antituberculosis,

anti-inflammatory, anti-helicobacter pylori activities and also in technological fields

like hair spray, photography polymers, electroplating, cosmetics, perfumes, printing

technology and environmental sciences. The most common method of obtaining

Schiff’s base is simple condensation of primary amines with aldehydes or ketones. In

addition, they have also been used as biological models of oxygen carriers. The

presence of thione groups makes them potential polydentate ligands and it is not

surprising that numerous thiosemicarbazide complexes have been prepared and

characterized. In addition, in the last few years there has been a growing attention

towards thiosemicarbazide related to their range of biological properties, specifically

1

INTRODUCTION ____________________________________________________________________________________________

as antifungal, antiviral, antibacterial and anticancer agents. Thiosemicarbazones are a

class of compounds obtained by condensation of thiosemicarbazide with suitable

aldehydes or ketones.

In recent years, it has been the trend to synthesize the ligand molecule having

definite frame work of donor atoms and to anchor them to different metal ions. Among

the coordination compounds, those derived from Schiff’s bases are of particular

interest. Schiff’s base ligands have been in the chemistry literature for over 150 years.

The literature survey clearly reveals that the study of this diverse ligand system is

linked with many of the key advances made in the field of inorganic chemistry.

Schiff’s bases can be characterized by IR, NMR, UV-Vis and mass spectral methods.

The C=N stretching frequencies of the ligands generally occur in the region 1680 and

1603 cm-1 when H, alkyl or aromatic groups are bound to C and N atoms. The nature

of different substituents on these atoms determines the position of the stretching

frequencies in the above range. For example, aryl groups on C and N atoms cause a

shift of the frequency towards the lower side of the range. A summary of typical IR

frequencies for various Schiff’s base ligands are available in the literature7. NMR

spectroscopy is very useful in understanding structural features of ligands in solution,

in particular keto-enol tautomerism found in these ligands [1,2].

[1] [2]

CN

OH

H

R CN

O

H

R

H

2

INTRODUCTION ____________________________________________________________________________________________

The interest in ligands has been driven, that they have been studied for a

considerable period of time for their biological properties. The heterocyclic

thiosemicarbazones derived from ketone have shown to present an interesting

pharmacological profile and it has been demonstrated that the presence of a bulky

group at terminals strongly improves their biological activity, probably due to

increase in lipophilicity8. Traces of interest to the beginning of the 20th century but

the first reports on their medical applications began to appear in the fifties as drugs

against tuberculosis and leprosy9. The activity of these compounds is strongly

dependent upon the nature of the heteroatom ring and the position of attachment of

thiosemicarbazone to the ring as well as the form of the thiosemicarbazone moiety.

These have been studied extensively due to their flexibility, selectivity and sensitivity

towards the central metal atom, structural and similarities with natural biological

substances and the presence of imine group (-N=CH-) which imparts the biological

activity10. The importance of metal complexes in the biological action of certain drugs

has been realized only in the past few decades. The metal complexes seem to best

upon the active sites of the drugs. It has been found that majority of the metal

complexes possessing biological activities are chelates, several reviews have been

reported, on the relationship of metal complexes to biological response.

1.2 COORDINATION NATURE OF THE LIGANDS

a) Monodentate Schiff’s base

It has been claimed that the basic strength of C=N group is not sufficient to

obtain stable complexes by coordination of the azomethine nitrogen atom to a metal

ion. Hence the presence of at least one other group is required to stabilize metal-

nitrogen bond. Aryl groups attached to either O or N generally stabilize the ligands by

3

INTRODUCTION ____________________________________________________________________________________________

resonance. For example monoamine Schiff’s bases such as N-(benzaldehydo)aniline

derivatives [3] are well known in the literature11.

[3]

The ligand [3] variously substituted in the phenyl rings, has been the most

extensively studied by NMR and X-ray analysis. 1H and 13C NMR spectra of some

BAAN derivatives have been reported. The azomethine proton was observed in the

region δ 8.41-8.50. These ligands exhibit solution spectral properties different from

their corresponding isoelectronic trans-azobenzene and trans-stilbene. These

differences are attributed to the non-planar structure of N-(benzaldehydo) aniline

BAAN derivatives in solution. Since the spectral properties are sensitive function of

the molecular conformation, systematic studies on the solid state structure have been

carried out. Furthermore, since the original work of Burgi and Dunitz12, many

workers have thought of utilizing the BAAN derivatives in crystal engineering

because of their thermochromism and photochromism properties. The geometrical

parameters defining the overall conformation of these Schiff bases and the geometry

of C=N moiety have been described in the literature.

b) Bidentate Schiff’s base

i) N, O donor atom set

Naveer et al.13 have reported a series of Co(II) and Ni(II) complexes of

bidentate ligand 4-oxo-4H-1-benzopyran-3-carboxyaldehyde-4-chloromethyl benzyl

hydrazone [4] where in the ligands is coordinated in enolized form. In this complex

OH

C

N

H

R2

R1

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INTRODUCTION ____________________________________________________________________________________________

CHN

C

O

O

O

M NNH

N

H2O

R

the four donor atoms N2 and O2 forms square base and two water molecules will be on

either side of the plane giving octahedral geometry around central metal atom.

M = Co(II) and Ni(II), Y = Cl and CH3 [4]

The mononuclear bidentate Schiff’s base salicylidene anthranilic acid and

bromosalcylidene acid [5] complexes of Cu(II),Ni(II), Zn(II), Co(II), Fe(III), Mn(II)

and Cd(II) have been reported by Patel et al.14. These complexes have been

characterized by elemental analysis, magnetic measurements, infrared spectra,

electronic spectra and thermo gravimetric analysis.

R = H and Br [5]

General structural formula and abbreviations of simple 2-pyridyloximes,

including methyl(2-pyridyl)ketoneoxime [(py)C(Me)NOH]. With only few exceptions

the hitherto structurally characterized metal complexes containing neutral 2-pyridyl

O

O

C NN C

OH

YH

O

O

CNNC

HO

YH

M OH2H2O

5

INTRODUCTION ____________________________________________________________________________________________

CR

N

H2CC

H H

CH2

N CR

oximes as ligands are mononuclear. The donor atoms of the neutral 2-pyridyl oximes

in metal complexes are the nitrogen atom of the oxime group and the nitrogen atom of

the pyridyl group. Thus, (py)C(R)NOH behave as N,N-chelating ligands making

necessary the employment of additional inorganic or organic anions to complete the

coordination sphere of the metal centre or to balance the charge of the complex

cation15.

ii) N, N donor atom set

The typical example may be bis(benzylidene)-1,2-diphenylethylenediamine

BADPH [6]. The structure and coordination behaviour of these ligands have been

extensively studied by Vogtle et al.16. The Schiff’s bases having two nitrogen atom

donors may be derived either from the condensation of dialdehydes or diketones with

two molecules of an amine or from reaction of diamines with aldehydes or ketones.

N N

[6]

Karmakar et al.17 have extensively studied the structure and coordination

behavior of pyridine-2-carboxaldehyde with 1,3-diaminopropane ligand [7]. The

Schiff’s base having two donor nitrogen atoms may be derived either from the

condensation of dialdehydes or diketones with two molecules of an imine or from

reactions of diamines with aldehydes and ketones.

6

INTRODUCTION ____________________________________________________________________________________________

N

OH

N C

H N

O

H2N

CH3HN

S

N

[7]

Transition metal complexes having oxygen and nitrogen donor Schiff’s bases

possess unusual configuration, structural lability and are sensitive to molecular

environment. The environment around the metal center ‘as coordination around the

geometry, number of coordinated ligands and their donor group’ is the key factor for

metalloprotein to carry out a specific physiological function. A large group of

bidentate Schiff’s bases having N, O donor atom set have been utilized as ligands for

metals, since oxygen is often present as an OH group, these ligands generally act as

chelating monoamines.

There are a number of examples of potential bidentate Schiff’s base ligands

with N, O donor sets derived18,19 from 2-amino-3-hydroxypyridine [8], 2-

isoproylaniline [9].

[8] [9]

c) Tridentate Schiff’s base

The Schiff’s base ligands may often acts as bridge between two metal center

giving polynuclear complexes of some tridentate Schiff’s base ligands20,21. These may

be generally considered as derived from the bidentate analogous by the addition of

another donor group. The tridentate Schiff’s base containing NO2, N2O, NSO and N2S

donor sets are given below [10], [11], [12] and [13].

7

INTRODUCTION ____________________________________________________________________________________________

N

N NH

O

R

N NH

O

RR1

OH

R = H, Cl, Br, CH3 R = R1 = H, Cl, Br, CH3

[10] [11]

R = CH3

N NH

SR

S

OH

N NH

SR

SH

OH

R = CH2C6H5

Keto (thione) form [12] Enol (thione) form [13]

d) Tetradentate Schiff’s base

Henri et al.22 have synthesized a tetradendate ligand [14] by reacting 2,3-

diaminopyridine with o-vanillin and their Cu(II), Ni(II), Ru(II), Zn(II), and Fe(III)

metal complexes containing two six membered rings.

[14]

Branca et al.23 have carried out an electron spin resonance spectral analysis of

Cu(II) complexes of bis(mercaptobenzylidene)diamine [15] and have arrived at the

8

INTRODUCTION ____________________________________________________________________________________________

S

N N(CH2)2

SCu

configuration around the Cu(II) ion, namely squareplanar. They have calculated the

various parameters using computer simulated programs.

[15]

An interesting recent advance in the tetradentate salen Schiff’s base chemistry

is Jacobson’s development of enantioselective olefin epoxidation catalysts24. Variety

of optically active salen complexes having substituted salicylaldehyde and chiral

ethylene diamine moieties are known to exhibit high degree enantioselectivities with

various olefinic substrates. Following is an example of Mn(III) complex [16] used in

asymmetric epoxidation catalysis.

[16]

Tetradentate Schiff’s bases with an N2O2 donor set have been widely studied

for their ability to coordinate metal ions. The properties of complexes obtained by

these ligands are determined by the electronic nature of the ligand as well as by its

conformational behaviour25. Tetradentate Schiff’s bases of ethylenediamine may be

mainly classified as (a) acen [17], (b) salen [18] and (c) moxen [19]

[42]

OO C

CMe

Me

HH

Me

MeC

C NN

[17] [43]

HOOH

NN

[18]

R

R

[44]

R

R

NN C

C

C

CN N

OHHO

[19]

HC N N

HC

O O

Mn

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INTRODUCTION ____________________________________________________________________________________________

Zohezzi et al.26 have reported the electrochemical properties of Schiff’s base

ligands of copper(II) complexes [20]. The Schiff’s base ligands studied gave the

cyclic voltammograms at 100 mVs-1 consists of a single cathodic peak potential

ranging from –1.6 to –2.0 V. No anodic wave occurred in the reverse scan. This

behaviour has been observed for a wide range of scan rates from 25 to 100 mVs-1.

Hence such reduction process should correspond to a totally irreversible electron

transfer. The cyclic voltammetric curves from the electrochemical reduction of the

studied copper(II) complexes exhibited a redox couple at potential in the range –0.91

to –1.28 V, which can be attributed to the reduction of the metal centre in the

complex.

R = OCH3, Br

[20]

Tetradentate N4 Schiff’s base ligands exhibiting chelating behaviour are also

called N4- macrocyles. These classes of ligands are of great interest because of their

resemblance to biochemically important porphyrins and corrins found in haemoglobin

and enzymes. Tetraazannulene(taenH2) [21] and tetraazacyclotetradecatetraene

(taenH2) [22] are the most common Schiff’s base N4-macrocycles.

C N N CH

HO

H

OH

RR

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INTRODUCTION ____________________________________________________________________________________________

[21] [22]

The electronic spectroscopic and magnetic properties of these compounds are

in accordance with square planar structures. An X-ray diffraction study of

[Me4(taen)Au]Cl2.H2O established that the [Me4(taen)Au]2+ cation adopts nearly a

planar structure with square planar Au(III) coordination geometry27.

Bis(dialkylglyoximato)en derivatives with N4 donor atoms, which can also form ring

systems as a result of intramolecular hydrogen bonding and exhibit macrocyclic

behaviour with metal centres are particularly attractive as models for vitamin B12. An

extensive series of mid and late transition metal (Me4taen) Mn+ complexes ,M =

Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and analogues containing differently substituted

taen2- ligands have been prepared28.

e) Pentadentate Schiff’s bases

A distorted pentagonal geometry has been observed in N,N′-(3-aza-1,5-

pentanediyl) bis(salicylidenimato) dioxouranium(IV), where five coordinated atoms

form a rather puckered pentagon29. Pentadentate Schiff’s bases can give Fe(II) and

Co(II) complexes which are relevant to the investigation of the stereochemical

changes accompanying oxygenation reaction. Metal complexes of the pentadentate

N

NH

HN

N

NH

N N

N

H

R2

R2

R1 R1

R2

R2

R1 R1

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INTRODUCTION ____________________________________________________________________________________________

ligands such as [23] and [24] have been widely investigated, and are shown to give

planar pentagonal coordination complexes with metal ions30.

[23] [24]

f) Hexadentate Schiff’s base ligands

Several potentially hexadentate ligands are known and these multidentate

ligands generally show tendency to form dinuclear metal complexes. The following

are some examples of hexadentate Schiff’s bases. The dianion of the Schiff’s bases

[25] and [26] are shown below are known to act as a hexadentate ligands in a variety

of metal complexes, thereby forming a distorted octahedral arrangement about the

metal atom. The two oxygen atoms occupy the cis positions while the four nitrogen

atoms (two cis amine and trans imine) complete the coordination sphere31,32.

[26]

OH

H

N(CH2)2NH(CH2)2NH(CH2)2N

HO

H

HO OH

N (CH ) 2 2 2 2 (CH ) N N N

[25] H H

12

INTRODUCTION ____________________________________________________________________________________________

N. Raman et. al., 33 have reported new Schiff’s base and their complexes of

Co(II), Ni(II), Cu(II) and Zn(II) derived from benzil-2,4-diphenylhydrazone with

aniline and characterized by magnetic susceptibility, IR, UV-vis., 1H NMR, CV and

EPR spectra. Based on the above analysis they assigned octahedral geometry to all the

complexes [27].

[27]

1.3 QUINAZOLINE CARBOTHIOHYDRAZIDE SCHIFF’S BASES

Quinazoline derivatives hold a place of significant in today’s world for their

important application in chemical, clinical and biological spheres. Medicinally

quinazoline has been used in various areas especially as an analgesic34, antioxidant35,

anticancer drugs36, anti-inflammatory37, anticonvulsant38, antibacterial39, antifungal40

and antimycobacterial agents41. It has also been found in the treatment of malaria42. In

spite of a large number of antibiotics and chemotherapeutics available for medical

use, the emergence of old and new antibiotics resistance developed in the last

decades, has created a substantial medical need for new classes of antimicrobial

agents43. Quinazoline derivatives have a therapeutic benefit as an anti- invasive agents

with potential activity in early and advanced solid tumors, metastatic bone disease and

leukemias44. Some of the known quinazoline derivative are reported to exhibit

Where, M = Cu(II), Co(II), Ni(II) and Zn(II) Ph = Phenyl

P h

N O 2

O2N N H N

C

P h

C

P h

N

M

P h

C

N

P h

C

N N H N O 2 P h

H 2 O O H 2

O2N

13

INTRODUCTION ____________________________________________________________________________________________

remarkable anticancer activity45. In addition several quinazoline derivatives posses

diverse biological activities viz. antimicrobial46, anticonvulsant47, hyponotics48,

diuretics49, antihypertensive50, antituberculor51.

Quinazoline and its derivatives are a class of hetero aromatic compounds that

have drawn much attention because of their biological and pharmaceutical activities

including a wide range of antitumor activity52. Anilinoquinazolines in particular are

potent inhibitors of Growth Factor Receptor (GFR) tyrosine kinases and have found

clinical applications in epidermal and vascular endothelial GFR targets53. Among

other pharmacological activities, quinazoline derivatives show remarkable

antimicrobial properties against microorganisms associated with death in patients

carrying immuno compromised diseases54. The anilinoquinazoline analogues are

experimental cancer therapeutics. The preparation of such targets proceeds via the

intermediacy of 4(3H)-quinazolinone, which is also active against microorganisms55.

The unique heterocyclic nitrogen compounds especially quinazolinone

derivatives are employed in many biological processes and as synthetic drugs56. The

quinazolin-4-one derivative is exploited in biological activities such as antifungal57.

8-hydroxyquinoline and quinazolin-4-one molecules into one molecule have not

received any attention in spite of well-defined applications of both the molecules.

Qunazolin-4-one, 8-hydroxyquinoline merged molecules as ligand and their

complexes with Cu(II), Ni(II), Co(II), Mn(II) and Zn(II) metal ion were studied for

antifungal activities58.

Fathalla et al.59 have synthesized one-pot quinazolin-4-yl-thiourea via N-(2-

cyano-phenyl)benzimidayl isothiocyanate and prepared the crystal structure of

1-phenyl-3-(2-phenyl quinazolin-4-yl)thiourea [28]. Alagarasamy et al.60 have

14

INTRODUCTION ____________________________________________________________________________________________

N

N

HN NH

S

synthesized novel 2-phenyl-3-(substituted methylamino)quinazoline-4-(3H)-ones[29]

and evaluated for their analgesic, anti-inflammatory and antibacterial activity.

[28] [29]

Aly, has synthesized and reported the biological activities of

triazinoquinazoline; quinazolinoquinazoline; pyrazolylquinazoline. A highly efficient

and versatile synthetic approach to the synthesis of annelated quinazoline derivatives

viz. 1,2,4-triazino[4]quinazoline, thiazolidinylquinazoline, quinazolino[4] quinazolin-

8-one and imidazoquinazolines, was presented. Also, a variety of pyrazolyl

quinazolines and pyrimidinylquinazolines, were obtained via. a sequence of

heterocyclization reactions of 4-methyl-N-[4-(4-oxo-3,4-dihydroquinazolin-2-yl)

phenyl]benzene-sulfonamide with different reagents61.

Khairy et al.62 has studied the chemistry of 4(3H)-quinazolinone. Many

derivatives of this system showed antifungal, antibacterial, anticancer, anti-

inflammatory, anticonvulsant, immunotropic, hypolipidemic, antiulcer, analgesic and

antiproliferative activities. The carbonyl and the cyano functions of these compounds

are suitably situated to enable reactions with common reagents to form a variety of

heterocyclic compounds. Also, the active methylene of cyanoacetamide can take part

in a variety of condensation and substitution reactions. Moreover, cyanoacetamides

and their related heterocyclic derivatives have generated great attention due to their

N

N

O

C6H5

N

H

CH2R

15

INTRODUCTION ____________________________________________________________________________________________

interesting biological, antiviral, antibacterial, herbicidal, plant growth regulators, anti-

inflammatory, anti-tumor and analgesic properties.

Shrivastava63 has reported the synthesis of some new 3-aryl(or alkyl)-2-

substituted mercapto-4-3(H)-quinazolines as antimalerial, antitubercular agents [30].

Quinazoline is benzo condensed pyrimidine, the first derivative was synthesized in

1969 denoted by term bicyanoamidobenzolyl [31] now known as 2-cyano-4-

quinazoline. The benzo condensed pyrimidines were prepared by Weddige64 in 1987.

[30] [31]

Mehta et al.65 synthesized quinazoline derivatives carrying potential

pharmacophores like thiazolidinone and isoxazole in an environmentally benign

microwave protocol. The yields of the products formed under MWI were high in

comparison to classical method and time required for completion of these reactions

was also less in comparison to classical method. By visualizing the antimicrobial data,

it could be observed that most of the final compounds exhibited moderate to strong

activities against microorganisms.

Vashi et al.66 synthesized the 6-bromo-2[(4-(2,3-dichlorophenyl))piperazine-

1-yl)methyl]-3-[8-hydroxyquinoline-5-yl]-3-quinazolin-4-one ligand and its transition

metal complexes and studied their antifungal activities. The ligand molecule acts as a

hexadentate in all the studied cases of complex. Octahedral structures for Ni(II),

Co(II) and Mn(II) complexes, tetrahedral polymeric structure for Zn(II) and distorted

octahedral for Cu(II) complex have been tentatively proposed. The substitutions of

N

NH

O

CN N

N

O

SR'

R

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INTRODUCTION ____________________________________________________________________________________________

CH3

C

H3C

CH3

NON

N

N

OM

NN

O

H3CC O

M = Co(II), Ni(II) and Cu(II)

N

O

H3C

N

CH3

SO

HN

COOH

COOHHN

N

O

H2N

CH3HN

S

N

phenyl rings by chlorine have much more effect on the fungicidal activity. The results

suggest that variation in structure on coordination affects the growth of micro

organisms and may result into inhibitory or reduction in toxicology of metal ions

towards some organisms.

Werbel and Degnan67 have reported the variety of analogues of 2,4-diamino-6-

[(aryl)thio] quinazolines with known antimalerial properties, via the inhibition of

DHFR enzyme, where in the 4-amino group was replaced by hydrazine and

hydroxylamine moieties. Such changes were found to markedly reduce the

antimalerial and antitumor properties [32], [33].

[32] [33]

Laxma Reddy et al.68 have reported the Co(II), Ni(II), Cu(II), Zn(II) and

Cd(II) complexes with 2,3-disubstituted quinazoline-(3H)-4-ones and characterized

by analytical, conductivity, thermal, magnetic, infrared, electronic, 1H NMR and ESR

data. The electronic spectral data suggest that the Co(II) and Ni(II) complexes are

octahedral geometry and Cu(II) complex is an distorted octahedral geometry, Zn(II)

and Cd(II) complexes are tetrahedral [34].

[34]

17

INTRODUCTION ____________________________________________________________________________________________

N

N

O

SH

N C Ar

H

Ar = Aldehydes

Jantova et al.69 have reported the in vitro antibacterial activity of ten series of

substituted quinazolines. The sensitivity of the gram positive bacteria to the tested

quinazolines was higher than that of gram negative bacteria.

Mamatha et al.70 have reported the Co(II), Ni(II), Cu(II), Zn(II), Pd(II) and

Cd(II) complexes of Schiff’s base derived from 3-amino-2-mercapto-quinazoline-4-

one and characterized by physico-chemical data and spectral studies [35].

[35]

Alkylating agents have been found no doubt as potent anticancer agents.

Nitrogen mustards are still playing a major role in the chemotherapy of cancer in spite

of newer chemotherapeutic agents. The capacity of these drugs to interfere with DNA

integrity and function in rapidly proliferating tissues provides the basis for their

therapeutic application. Quinazolinone derivatives exhibit a wide range of activities

such as antibacterial, anthelmintic, neuroleptic. Antitumor activities of 2, 3-dihydro-2-

aryl-4-quinazolinones were reported. A more recent re-evaluation of this type of

compound by NCI against human tumor cell lines reconfirmed that, like colchicines,

they are effective inhibitors of tubulin polymerization. 1, 6, 8-trisubstituted

quinazolinones with a nitrogen mustard moiety connected through methylene group at

position 2 have been synthesized and found to show better anticancer activity71.

Kumar et al.72 have reported the 3-amino-2-methylquinazoline-4(3H)-2',4'-

dinitrophenyl hydrazones and its complexes of Cr(III), Mn(II), Cd(II), Co(II), Ni(II),

18

INTRODUCTION ____________________________________________________________________________________________

S

O

H

CN C

N Co

OH2

Cl

S H

OC N

CN

NO2

NO2

NH

N

N

N NH2

CH3

Cu(II), Fe(II) and Zn(II). All these complexes were characterized on the basis of

elemental analysis, molar conductance, magnetic susceptibility, IR, electronic,

1H NMR, ESR and TGA [36].

[36]

Pandey et al.73 have synthesized the VO(II), ZrO(II), Zr(II), Nb(II) and Ta(V)

complexes using the ligands 2-mercapto-3-subsituted–quinazoline-4-one [37] and

characterized by physico-chemical techniques to identify the structure for all the

complexes.

[37]

Singh et al.74 have prepared and charecterized the complexes of Co(II), Zn(II),

Cd(II) and Hg(II) with 2-mercaptoquinazole-4-one, which contains two potential

donor sites. The Co(II) complex forms an octahedral geometry, its electronic

spectrum and diamagnetism favors an octahedral configuration [38].

[38]

NH

C

O

R

S

R = H, C6H5

19

INTRODUCTION ____________________________________________________________________________________________

N

OC

O

CH3

I

Kumar and Sharma75 have synthesized Cr(II), Co(II), Ni(II), Zn(II), Cd(II)

and Hg(II) complexes using substituted quinazoline-(3H)-4-ones [39] and

characterized on the basis of magnetic and spectral properties.

[39]

Amine et al.76 have synthesized 1-(2-heptadecyl-4-oxoquinazoline-3(4H)-

yl)thiourea [40] and studied surface active properties, industrial application and the

biodegradability of some of the synthesized compounds.

[40]

Singh et al.77 have reported the 6-iodo-2-methyl-4H-benzo[d][1,3]oxazin-4-

one[41] and its derivative 3-anilino-2-methyl-6-iodoquinazolin-4-(3H)-one, which

shows as insecticidal and antimicrobial activities. The compounds were characterized

by elemental analysis, IR, 1H NMR and mass spectrometry.

[41]

Tyagi et al.78 have reported the 3-(aminoacetylthiosemicarbazido)-2-

methylmono-substituted quinazolin-4(3H)-ones, which shows a very good blood

N

N

O

R O

OR'

Br

N

N N CH

C6H5

O

OCH3

HO

20

INTRODUCTION ____________________________________________________________________________________________

N

NC

O

R

NH C NH2

S

N

NC

O

CH3

NHCOCH2HNNHCNH2

S

CH RX

N

NC

O

S

HN

CH3

RHN

S

R1

pressure lowering activity and characterized by elemental analysis, IR and 1H NMR

studies [42].

[42]

Fathalla et al.79 have reported the quinazolin-4-yl-thiourea[43] The structures

of products were confirmed by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and

X-ray crystallographic data.

[43]

Rashood et al.80 have synthesized some new 4(3H)-quinazolinone analogues

and evaluated for their dihydrofolate reductive inhibition, antitumor testing and

molecular modeling study. The compounds were confirmed on the basis of elemental

analysis, 1H NMR, 13C NMR and TLC [44].

[44]

1.4 QUINOLINES

Baltork et al,81 have reported the series of 2,4-disubstituted quinolines

through a one-pot reaction of structurally diverse 2-aminoaryl ketones with various

arylacetylenes in the presence of K5CoW12O40 .3H2O as a reusable and

21

INTRODUCTION ____________________________________________________________________________________________

environmentally benign catalyst under microwave irradiation and solvent free

conditions[45].

O

NH2

R'

R +Ar

K5CoW12O40.3H2Oheat, MW(1000W)1100C, 5-20min

R

N

R'

Ar

[45]

Thakur et al.82 have prepared the quinoline nucleus in which the primary

arylamine was taken as starting compound and its acetylation occurs by the treatment

with the acetic anhydride. The resulting aryl acetamide is further cyclized by the

treatment with the Vilsmeier–Haack reagent (DMF + POCl3) which results the

quinoline nucleus with primary aldehyde [46]. This aldehyde group is turned to

Schiff’s base after the treatment with substituted anilines and gives the various

derivatives.

Thomas et al.83 have reported the design, synthesis and docking studies of

new quinoline-3-carbohydrazide derivatives as antitubercular agents. The synthesized

compounds were characterized by spectral and elemental analyses. The structure of

synthesized compound was evidenced by X-ray crystallographic study. The

synthesized compounds were evaluated for their antimicrobial activities including

antimycobacterial activity. Amongst the tested compounds, displayed promising

NH2

Ac2O

HCl, NaHCO3 NH

O

reflux DMF/POCl3

N

CHO

Cl

H2NR

C2H5OH, AcOHN

HC

Cl

NR

46

22

INTRODUCTION ____________________________________________________________________________________________

antimicrobial activity. The mode of action of these active compounds was carried out

by docking of receptor enoyl-ACP reductase with synthesized ligands.

Sakai et al.84 have reported the novel copper-catalyzed annulation of

2-ethynylanilines with an N, O-acetal, gives quinoline derivatives with an ester

substituent on the 2-position. A combination of CuBr2 and trifluoroacetic acid (TFA)

promotes a annulation of 2-ethynylaniline with ethyl glyoxylate in the presence of

piperidine [47].

[47]

Rajakumar and Raja85 have reported the synthesis of 2-chloroquinoline-3-

carbaldehydes from acetanilides via a Vilsmeier-Haack reaction either by traditional

methods or by microwave or ultrasonic irradiation [48].

Me NH

OR POCl3/DMF, 00C

80-90 0C, 5hN Cl

CHO

R

R = alkyl, alkoxy, halo

[48] Jacob et al.86 have reported cobalt-catalyzed selective conversion of

diallylanilines to quinolines and the cross-coupling of arylimines with diallylanilines

to generate quinolinesn[49].

HN

R

10% Co2(CO)8

CO (1atm)THF, 850C

N

R

+R

NH2

[49]

23

INTRODUCTION ____________________________________________________________________________________________

Mistry and Jauhari have developed a novel, efficient and potent quinoline

based azitidinone and thiazolidinone analogues. Quinoline nucleus is one of the active

constituents present in many standard drugs and is known to increase in

pharmacological activity of the molecules. The presence of substituted amines is also

instrumental in contributing the net biological activity. Briefly, high potency has been

observed with the final scaffolds in the form of azitidinones and thiazolidinones

bearing various amines containing halogen(s) such as chloro or fluoro and nitro

functional groups. They indicated that quinoline based thiazolidinones are more

efficious antimicrobial agents compared to quinoline based azitidinone analogues87.

Mujalda et al.88 have reported the synthesis of 1-[2-hydroxyl–5–(substituted

phenyl)diazyl benzylidene-3-(4-oxo-2-phenylquinazolin-3(4H)-yl)thiourea [50].

A mixture of the appropriate, 2-hydroxy –5–(phenyldiazenyl) benzaldehyde and N-[2-

phenyl-4(3H)-oxo-quinazoline-3-yl] thiourea were refluxed in DMF. The mixture was

then cooled in an ice bath and the product separated was repeatedly washed with

water followed by ethanol and recrystallised from diethyl ether.

Dawane et al.89 have described a simple method for the synthesis of

substituted benzilidine-3-(4,5-diphenyl-1H-.imidazol-2-yl)-6-methyl-quinoline. The

synthesized compounds were confirmed by the spectral analysis and further evaluated

for their antimicrobial activity. The antibacterial and antifungal activity revealed that

most of the compounds showed moderate to good activity.

N

N

C6H5

O

NH C

S

N

H

N

HO

N

R

[50]

24

INTRODUCTION ____________________________________________________________________________________________

1.5 COUMARINES

Alonso et al.90 have reported the several new ionophores derived from crown

ethers and iminodiacetic subunits attached to 3-aroylcoumarins and fully

characterized [51]. The alkaline-earth complexes of these ligands were studied from

their UV–visible and fluorescence data. Some systems displayed strong bathochromic

shifts upon complexation with Mg2+ that may make them useful signaling devices of

this cation.

Ajania and Nwinyib91 have described an exploration of potential utilization

of microwaves as an energy source for heterocyclic synthesis using condensation of

3-acetylcoumarin with aromatic and heteroaromatic aldehydes to afford the

corresponding aromatic chalcones and heteroaromatic chalcones, respectively, in

good to excellent yield within 1–3 minute [52]. The chemical structures were

confirmed by analytical and spectral data. All the synthesized compounds were

screened for their antibacterial activity and 3-{3-(4-dimethylaminophenyl)acryloyl}-

2H-chromen-2-one was discovered to be the most active at minimum inhibitory

concentration (MIC) value.

O O

O

O

O

Et2N

O

OO

Mg2+

[51]

25

INTRODUCTION ____________________________________________________________________________________________

Cacic et al.92 synthesized a series of Schiff’s bases (E)-N-2-aryliden-2-(4-

methyl-2-oxo-2H-chromen-7-yloxy)acetohydrazides and novel N-(2-(substituted

phenyl)-4-oxo-thiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamides

and evaluated for antioxidant activity by phosphor molybdenum method. The

1,3-thiazolidine-4-one derivatives containing the coumarin moiety were synthesized

by cyclocondensation of the Schiff's bases and mercapto acetic acid. Compounds

which are indicated as already known are resynthetized and the analytical data

obtained for these compounds were comparable, but slightly different from those of

other authors. For all the novel compounds structures were elucidated by means of

various spectral methods. Two of the Schiff’s bases and three of 1,3-thiazolidine-4-

ones proved to have better antioxidant activity in comparison with ascorbic acid. In

conclusion, it is evident that the substituents on the phenyl ring have a great influence

on antioxidant activity.

Considering the vast applications of the complexes of quinazolines, quinolines

and coumarin moieties, it was planned to synthesise, characterize and study the

biological activities of the complexes of quinazolines, quinolines and coumarin

moieties with Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II).

CHO

OH

+ CH3COCH2CO2C2H5Piperidine

MWO

CH3

O

O[52]

26

INTRODUCTION ____________________________________________________________________________________________

1.6 AIMS AND OBJECTIVES OF THE PRESENT INVESTIGATION

The present study is concerned with the synthesis, characterization and

biological activities of some metal complexes with Schiff’s base ligands using

methylquinazoline carbothiohydrazide, methylquinazoline hydrazide and

phenylquinazoline carbothiohydrazide moieties. The metal chlorides were used for

preparing the complexes. Characterization of these complexes have been carried out

on the basis of elemental analysis, electronic spectra, IR, 1H NMR, magnetic

susceptibility, ESR, molar conductivity, TGA, powder X-ray diffraction and

biological activity studies.

THE THESIS DIVIDED INTO SIX CHAPTERS

CHAPTER - I: INTRODUCTION

This chapter deals with the literature survey of the ligand and complexes

containing quinazolines, quinolines and coumarin moieties and their applications.

CHAPTER - II: EXPERIMENTAL

This chapter deals with the experimental procedures followed for the synthesis

of the various Schiff’s base ligands such as L1 = [(2-hydroxyquinolin-3-yl)

methylidene]-2-methyl-4-oxoquinazoline-3(4H)-carbothiohydrazide, [HQMMOQC];

L2 = [(6-bromo-2-hydroxyquinolin-3-yl)methylidene]-2-methyl-4-oxoquinazoline-3

(4H)-carbothiohydrazide, [BHQMMOQC]; L3 = [(2-hydroxy-6-methoxyquinolin-3-

yl)methylidene]-2-methyl-4-oxoquinazoline-3(4H)-carbothiohydrazide, [HMeQMMO-

-QC]; L4 = 3-[(2-hydroxyquinoline-3-ylmethylene)-amino]-2-methyl-3H-quinazoline-

4-one, [HQMAMQ]; L5 = 3-[(2-hydroxy-6-methylquinoline-3-ylmethylene)-amino]-2-

methyl-3H-quinazoline-4-one, [HMQMAMQ]; L6 = 3-[(2-hydroxy-6-methoxyquinoli -

27

INTRODUCTION ____________________________________________________________________________________________

-ne-3-ylmethylene)-amino]-2-methyl-3H-quinazoline-4-one, [HMeQMAMQ]; L7 = 4-

oxo-[(2-oxo-2H-chromen-3-yl)ethylidene]-2-phenylquinazoline-3(4H)-carbothiohydra-

-zide, [OOCEPQC]; L8 = 6-bromo-[(2-oxo-2H-chromen-3-yl)ethylidene-4-oxo]-2-

phenylquinazoline-3(4H)-carbothiohydrazide, [BOCEOPQC]; L9 = 6-methoxy-[(2-

oxo-2H-chromen-3-yl)ethylidene-4-oxo]-2-phenylquinazoline-3(4H)-carbothiohydrazi-

-de, [MeOCEOPQC] and their Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and

Hg(II) complexes.

CHAPTER - III : SYNTHESIS AND CHARACTERIZATION OF Mn(II), Co(II),

Ni(II), Cu(II), Zn(II), Cd(II) AND Hg(II) COMPLEXES OF

METHYLQUINAZOLINE CARBOTHIOHYDRAZIDE SCHIF-

-F’S BASE LIGANDS L1 = [HQMMOQC], L2 = [BHQMMOQC]

AND L3 = [HMeQMMOQC].

This chapter deals with the characterization of Schiff’s base ligands , L1 = [(2-

-hydroxyquinolin-3-yl)methyllidene]-2-methyl-4-oxoquinazoline-3(4H)-carbothiohy-

-drazide, [HQMMOQC]; L2 = [(6-bromo-2-hydroxyquinolin-3-yl)methylidene]-2-

methyl-4-oxoquinazoline-3(4H)-carbothiohydrazide, [BHQMMOQC]; L3 = [(2-

hydroxy-6-methoxyquinolin-3-yl)methylidene]-2-methyl-4-oxoquinazoline-3(4H)-

carbothiohydrazide, [HMeQMMOQC] and their Mn(II), Co(II), Ni(II), Cu(II),

Zn(II), Cd(II) and Hg(II) complexes.

CHAPTER - IV : SYNTHESIS AND SPECTRAL CHARACTERIZATION OF

Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) AND Hg(II)

COMPLEXES OF METHYL QUINAZOLINE HYDRAZIDE

SCHIFF’S BASE LIGANDS L4 = [HQMAMQ] , L5 =

[HMQMAMQ] AND L6 = [HMeQMAMQ]

This chapter deals with the synthesis and characterization of Schiff’s base

ligands, L4 = 3-[(2-hydroxyquinoline-3-yl-methylene)-amino]-2-methyl-3H-quinazoli

28

INTRODUCTION ____________________________________________________________________________________________

ne-4-one, [HQMAMQ]; L5 = 3-[(2-hydroxy-6-methylquinoline-3-ylmethylene)

amino]-2-methyl-3H-quinazoline-4-one, [HMQMAMQ]; L6 = 3-[(2-hydroxy-6-meth

oxyquinoline-3-ylmethylene)-amino]-2-methyl-3H-quinazoline-4-one, [HMeQMAM

Q] and their Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) complexes.

CHAPTER - V : SYNTHESIS AND CHARACTERIZATION OF Mn(II), Co(II),

Ni(II), Cu(II), Zn(II), Cd(II) AND Hg(II) COMPLEXES OF

PHENYL QUINAZOLINE CARBOTHIOHYDRAZIDE SCHIFF’S

BASE LIGANDS L7 = [OOCEPQC], L8 = [BOCEOPQC] AND

L9 = [MeOCEOPQC]

This chapter deals with the characterization of Schiff’s base ligands such as

L7 = 4-oxo-[(2-oxo-2H-chromen-3-yl)ethylidene]-2-phenylquinazoline-3(4H)-carbot-

-hiohydrazide, [OOCEPQC]; L8 = 6-bromo-[(2-oxo-2H-chromen-3-yl)ethylidene-4-

oxo]-2-phenylquinazoline-3(4H)-carbothiohydrazide, [BOCEOPQC]; L9 = 6-metho-

-xy-[(2-oxo-2H-chromen-3-yl)ethylidene-4-oxo]-2-phenylquinazoline-3(4H)-carboth-

-iohydrazide, [MeOCEOPQC] and their Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II)

and Hg(II) complexes.

CHAPTER-VI: ANTIMICROBIAL ACTIVITY AND DNA CLEAVAGE

STUDIES

This chapter deals the antimicrobial activity studies of the Schiff’s base

ligands L1 to L9 and their Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)

complexes. All the Schiff’s base ligands and complexes were tested for the

antibacterial and antifungal activity against E. coli, S. aureus, A. niger and A. flavous

following the cup-plate method. This chapter also deals the DNA cleavage activity

studies of Schiff’s base ligands L1, L2 and L3 and their Mn(II), Co(II), Ni(II), Cu(II),

Zn(II) and Cd(II) metal complexes.

29

INTRODUCTION ____________________________________________________________________________________________

1.7 REFERENCES

1] G.B. Kauffman in "Inorganic Coordination Compounds", Heyden & Son Ltd,

(1981).

2] G. Manoussakis, C. Bolas, L. Eateriniatadou and C. Sarris, J. Med. Chem., 22,

421, (1987).

3] R.K. Parashar, R.C. Sharma, A. Kumar and G. Mohan, Inorg. Chim. Acta., 151,

201, (1988).

4] S. Suma, M.R.S. Kumar, C.C.R. Nair and C.P. Prabhakaran, Indian J.

Chem., 32(A), 241, (1993).

5] L. Mishra, A. Jha and A.K. Yadav, Trans. Met. Chem., 22, 406, (1997).

6] D.U. Warad, C.D. Satish, V.H. Kulkarni and C.S. Bajgur, Indian J. Chem.,

39(A), 415, (2000).

7] U. Casellato, P.A. Vigto and M.V. Vidali, Coord. Chem. Rev., 23, 31, (1977).

8] C. Sheikh, M.S. Hossain, M.S. Easmin, M.S. Islam and M. Rashid, Biol. Pharm.

Bull., 27, 710, (2004).

9] G. Pelosi, J. Open Crystallography, 3, 16, (2010).

10] R. Yamgar, P. Kamat, D. Khandekar and S. Sawant, J. Chem. Pharm. Res., 3(1),

188, (2011).

11] W. Smith, ‘The Chemistry of Carbon-Nitrogen Double Bond’, Wiley-

Interscience, New York, .239, (1970).

30

INTRODUCTION ____________________________________________________________________________________________

12] H.B. Burgi and J.D. Dunitz, Helv. Chim. Acta, 53, 1747, (1970).

13] N. Naveer, M.A. Khaltub, M.M. Bekheit and A.H. Kaddah, Indian J. Chem.,

35(A), 308, (1996).

14] K.M. Patel, N.H. Patel, K.N. Patel and M.N. Patel, J. Indian Coun. Chem., 17(1),

19, (2000).

15] G. Constantinos, S.P. Perlepes and C.P. Poulou, Bioinorg. Chem. and Appl.,

ID 960571, 9, (2010).

16] F. Vogtle and E. Goldsmith, Angew. Chem. Int. Ed. Engl., 14, 520, (1974).

17] T.K. Karmakar, B.K. Ghosh, H.K. Fun and S.K. Chandra, Indian J. Chem.,

45(A), 1356, (2006).

18] F. Chang, G. Xu, J. Li, H. Song and W.H. Sun, J. Organomett. Chem., 689, 936,

(2004).

19] K.B. Gudasi, G.S. Nadagouda and T.R. Goudar, J. Indian Chem. Soc., 83, 376,

(2006).

20] S. Pal, Proc. Indian Acad. Sci., 114(4), 417, (2002).

21] N.R. Pramanik, S. Ghosh, T.K. Raychaudhuri, S. Ray, R.J. Butcherand and

S.S. Mandal, Polyhedron, 23, 1595, (2004).

22] W. Henri, L. Kam, J. Tagenine and B.M. Gupta, Indian J. Chem., 40A, 999,

(2001).

23] M. Branca, P. Sacconi and B. Pispisa, J. Chem. Soc. Dalton, 4, 81, (1976).

31

INTRODUCTION ____________________________________________________________________________________________

24] E.N. Jacobson, W. Zhang and W.L. Guler, J. Am. Chem. Soc., 113, 6703, (1991).

25] F. Lions and K.V. Mortin, J. Am. Chem. Soc., 79, 2733, (1957).

26] S. Zohezzi, E. Spodine and A. Deciuti, Polyhedron, 21, 55, (2002).

27] J.H. Kim and G.W. Everett, J. Inorg. Chem., 20, 853, (1981).

28] M. Funjwara, H. Wakia, T. Masushia and T. Shono, Bull. Chem. Soc. Japan, 63,

3443, (1991).

29] F. Benetollo, G. Bombieri and A.J. Smith, Acta. Cryst., B35, 3091, (1979).

30] V.L. Goedken and G.G. Christoph, Inorg. Chem., 12, 2316, (1973).

31] E. Sinn, G. Sim, E.V. Dose, M.F. Tweedle and L.J. Wilson, J. Am. Chem. Soc.,

100, 3375, (1978).

32] P.D. Cradwick, M.E. Cradwick, D. Hall and T.N. Waters, Acta. Cryast., B28, 45,

(1972).

33] N. Raman, S. Ravichandran and C. Thangaraja, J. Chem. Sci., 116, 15, (2004).

34] K.M. Amin, M.M. Kamel and M.M. Anwar, Eur. J. Med. Chem., 45, 2117,

(2010).

35] J. Vijaynathappa and S. Bhojraj, J. Health Sci., 54, 24, (2008).

36] P. Manihandrika and V. Sridhar, Indian J. Chem., 48B, 840, (2009).

37] V. Chandregowda, A.K. Kush and G.C. Reddy, Eur. J. Med. Chem., 44, 3046,

(2009).

32

INTRODUCTION ____________________________________________________________________________________________

38] R.S. Giri, H.M. Thaker and T. Giordano, Eur. J. Med. Chem., 44, 2184, (2009).

39] D. Vachala and H. Unnissa, Indian J. Heterocycl. Chem., 17, 347, (2008).

40] Y. Kabri, A. Nadine and A.L. Dumetre, Eur. J. Med. Chem., 45, 616, (2010).

41] A. Ashraf, G. Sami, A. Hamide, A.M. Al-Obaid and H.I. El-Subbagh, Arch.

Pharm. Med. Chem., 2, 95, (2003).

42] J. Guan, Q. Zhang, M. O'Neil, N. Obaldia, A. Ager, L. Gerena and A.J. Lin,

Antimicrob. Agents Chemother., 49(12), 4928, (2005).

43] S. Singh, F. Athar, M.R. Maurya and A. Azam, Eur. J. Med. Chem., 41, 592,

(2006).

44] G. Aguirre, L. Boiani, H. Cerecetto, L. Oteroe, C. Rigol, C.O. Azar and M.

Faundez, Biorg. Med. Chem., 17, 4885, (2004).

45] A.S. Dobek and E.T. Diskson, Antimicrob. Agents and Chemotherapy, 18, 21,

(1980).

46] D.J. Klayman and J.P. Bartoservich, J. Med. Chem., 22, 855, (1997).

47] S. Offiong and S. Martelli, Farmaco., 49, 513, (1994).

48] E. Bermejo and C. Wesst, Polyhedron, 18, 3695, (1999).

49] P.M. Loiseau and D.X. Nguyen, Trop. Med. Treat. Health, 1(3), 379, (1996).

50] V. Kumar, A. Kukshal, P. Rathee and S. Rathee, Res. J. Pharma. Bio. Chem., 1,

98, (2010).

33

INTRODUCTION ____________________________________________________________________________________________

51] A.J. Quiroga, M. Perez, R. Masaguer and P. Roman, J. Med. Chem., 41, 1399,

(1998)

52] P.M. Traxler, Expert Opinion on Therapeutic Patents, 7, 571, (1997).

53] I. Collins and P. Workman, Curr. Signal Transduc. Ther., 1, 13, (2006).

54] A.E. Wakeling, Endocr. Relat. Cancer, 12, 183, (2005).

55] T. Herget, M. Freitag, M. Morbitzer, R. Kupfer, T. Stamminger and M. Marschall,

Antimicrob. Agents Chemother., 48, 4154, (2004).

56] N.B. Patel and R.C. Chaudhari, J. Ind. Chem. Soc., 83, 838, (2006).

57] R.T. Vashi, S.B. Patel and H.K. Kadiya, Der. Pharma. Chemica, 2(1), 109,

(2010).

58] R.T. Vashi, C. D. Shelat and H. Patel, Int. J. Appl. Biol. and Pharm. Tech., 1(3),

883, (2010).

59] W. Fathalla, M. Cajan, J. Marek and P. Pazdera, Molecules, 6, 588, (2001).

60] V. Alagarsamy, R. Revathi and V. Nayanan, Indian J. Pharm. Sci., 5, 34, (2003).

61] A.A. Aly, J. Chin. Chem. Soc., 54(2), 437, (2007).

62] A.M. Khairy, M.M. Aly, Y.A. Mohamed, W.M. Basyouni and S.Y. Abbas,

World J. Chem., 4(2), 161, (2009).

63] K.S.L. Srivastava, Indian J. Pharm., 32, 97, (1970).

34

INTRODUCTION ____________________________________________________________________________________________

64] J. Weddige, J. Prakt. Chem., 31(2), 124, (1885).

65] S. Mehta, N. Swarnkar, M. Vyas, J. Vardia, P.B. Punjabi and S.C. Ameta, Bull.

Korean Chem. Soc., 28(12), 2338, (2007).

66] R.T. Vashi, C.D. Shelat and H. Patel, Inter. J. Appl. Biol. and Pharm. Tech., 1(3),

883, (2010).

67] L.M. Werbel and M.J. Degnan, J. Med. Chem., 30, 2151, (1987).

68] K. Laxma Reddy, S. Srihari and P. Lingaiah, Indian J. Chem., 24(A), 318, (1985).

69] S. Jantova, S. Stankovsky and K. Spirkova, Biologia Bratislava, 59(6), 741,

(2004).

70] K. Mamatha, B. Rupini and S. Srihari, J. Indian Chem. Soc., 81, 950, (2004).

71] Y. Govindaraj, S. Moorthy, V. Karthikeyan, V. Agrahari, S. Gupta and R.K.

Nema, Acad. J. Canc. Research, 2(2), 73, (2009).

72] M. Kumar, H.R. Mahato, V. Sharma and T. Sharma, J. Indian Chem. Soc., 66, 73,

(1989).

73] R.N. Pandey, R.N. Sharma, L.M. Roy and P. Sharma, J. Indian Chem. Soc., 69,

719, (1992).

74] M. Kumar and T. Sharma, J. Indian Chem. Soc., 68, 539, (1991).

75] B. Singh, M.M.P. Rukhaiyar and R. J. Sinha, J. Inorg. Nucl. Chem., 39, 29,

(1977).

35

INTRODUCTION ____________________________________________________________________________________________

76] M.A. Amine, A.A. Aly and R.E. Sayed, Indian J. Chem., 45(B), 1020, (2006).

77] T. Singh, S. Sharma, V.K. Srivastava and A. Kumar, Indian J. Chem., 45(B),

2558, (2006).

78] M. Tyagi, V.K. Srivastava, R. Chandra and A. Kumar, Indian J. Chem., 41(B),

2367, (2002).

79] W. Fathalla, M. Cajan, J. Marek and P. Pazdera, Molecules, 5, 598, (2003).

80] S.T.A. Rashood, I.A. Aboldahab, M.N. Nagi, L.A. Abouzeid, S.G.A. Hamide,

K.M. Youssef, A.M.A. Obaid and H.I.E. Subbagh, Bioorg. Med. Chem., 14,

8608, (2006).

81] I.M. Baltork, S. Tangestaninejad, M. Moghadam, V. Mirkhani, S. Anvar and A.

Mirjafari, Synth. Lett., 3104-3112 (2010).

82] A.S. Thakur, A.K. Jha, P. Verma, D. Devangan and A. Chandy, Int. J. Comp.

Parm., 3(13), 1, (2010).

83] K.D. Thomas, A.V. Adhikari, S. Telkar, N.K. Pal, G. Row and E. Sumesh, Eur.

J. Med. Chem., 46(11), 5283, (2011).

84] N. Sakai, K. Tamura, K. Shimamura, R. Ikeda and T. Konakahara, Org. Lett., 14,

836, (2012).

85] P. Rajakumar and R. Raja, Tetrahedron Lett., 51, 4365, (2010).

86] J. Jacob, C.M. Cavalier, W.D. Jones, S.A. Godleski and R.R. Valente, J. Mol.

Cata. A: Chem., 182, 565, (2002).

87] B. Mistry and S. Jauhari, Arch. Appl. Sci. Res., 2(6), 332, (2010).

36

INTRODUCTION ____________________________________________________________________________________________

88] V. Mujalda, S. Tiwari, V. Sharma, P. Saxena and M. Shrivastava, Int. J. Chem.

Tech. Res., 4(3), 1033, (2012).

89] B.S. Dawane, S.S. Chobe, G.G .Mandawad, B.M. Shaikh, S.N. Kinkar and S.R.

Chavan, Arch. Appl. Sci. Res., 3(1), 401, (2011).

90] M.T. Alonso, O. Juanes and J.C. Ubis, J. Photochem. and Photobiol. Chem., 147,

113, (2002).

91] O.O. Ajania and O.C. Nwinyib, J. Heterocyclic Chem., 47, 179, (2010).

92] M. Cacic, M. Molnar, B. Sarkanj, E.H. Schon and V. Rajkovic, Molecules, 15,

6795, (2010).

37