research & reviews a journal of drug design & discovery (vol1, issue1)

Research & Reviews: A Journal of

Drug Design & DiscoveryRRJoDDD

Jan - April 2014

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STM JOURNALS

1. Drug Designing and Research: Ayurvedic Approach Nishant Shukla 1

2. Synthesis and Anti-Bacterial Activity Profile of Cyclized Diazonium Compounds Priti Jain, L. Naga Rajiv, Hemant R. Jadhav 4

3. Targeting Cancer through Angiogenesis Inhibition: Prospective of Azole Based Small MoleculesPratap Chandra Acharya 13

ContentsResearch & Reviews: A Journal of Drug Design & Discovery

RRJoDDD (2014) 1-3 © STM Journals 2014. All Rights Reserved Page 1


Volume 1 Issue 1

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Drug Designing and Research: Ayurvedic Approach

Nishant Shukla*

Morjand Khari, Sriganganagar, Rajasthan

Abstract Ayurveda the ancient Indian medical wisdom has served society through its holistic

approach of healing. Ancient Indian scientists Acharya Charaka, Acharya Sushruta, etc. has done in drug research and clinical research. This approach was not only aims

to treat a person but to bring the original state. Acharya Charaka clarifies that a

physician or researcher ought to look at least four whilst treatment the patient i.e. roga bala (therapeutic effect on disease), deha bala (strength or immunity), chitta bala

(psyche) and agni bala (digestion & metabolism). Herbs used ought to have at least four properties i.e. bahu kalpap, bahu gunam, sampanna and yogya. Preparation of

poly-herbal, herbo-mineral combination ought to be done as per the norms prescribed

by Acharya Charaka. Individualized approach of drug delivery is necessary and research needs to incorporate them. The paper discuss these in details.

Keywords: Ayurveda, Drug designing, poly-herbal, herbo-mineral

*Author for Correspondence E-mail: [email protected]

INTRODUCTION Drug designing is extremely important in

medical research. It is even more important in

Ayurveda system of medicine, where

numerous combination herbal, herbo-minerals,

herb-animal compounds are prepared and

used. Effect of individual drugs were studied

and documented in ancient classics like

Charaka Samhita, Sushruta Samhita, Astang

Hridya, Nighantus, etc. latest work done in this

field is by Acharya Bhavmishra in 18th

century. Many combinations were made by

different scholar in past based on their

observations and experiences, this is practiced

in present era also to search for better

alternate.

Owing to the fact that diseases are always

multifactorial and group of symptoms instead

of using single herb combinations were

prepared and experimented. Today there are

more than ten thousand poly-herbal, herbo-

mineral compound in use for ayurvedic

medical management. The quest is continuing,

and new formulations are prepared,

experimented, used clinically.

Drug designing requires detailed study of

human body and drugs used. Human body is

not physical only; psyche affects body’s

physiology as body & mind are

interdependent. One must attend to holistic

approach while preparing any new poly-herbal

or herbo-mineral combination. Other primary

requisite mentioned in the classics is a drug

must treat disease and at the same time should

not alter other doshas. In order to achieve the

above mentioned goal Acharya Charaka gave

guidelines i.e. physician must examine at least

four aspects very minutely whilst treating

patient i.e. yoga Bala (strength/severity/gravity

/stage of disease), Deha Bala (body strength &

immunity), Chitta Bala (psychological

wellbeing) and Agni Bala (digestion &

metabolism)[1]. This paper will highlight

ayurvedic principles for designing a poly-

herbal medicine.

KNOWLEDGE AND RESEARCH

GAPS Preparation of SOP (standard operative

procedure) for Designing of poly-herbal

formulation is ought to be made from the

guidelines described in ayurvedic classics.

This is hurdle in scientific approach of drug

planning.

http://www.stmjournals.com/

Drug Designing & Research Nishant Shukla

__________________________________________________________________________________________


AIMS AND OBJECTIVE A review paper on scientific designing of

poly-herbal ayurvedic medicines was

presented with following aims & objectives

1. Study of ayurvedic principle for drug

research

2. SOP for drug designing

MATERIALS & METHODS Review paper was based on scientific

evidences available in ancient ayurvedic

classics and it’s through study and develops a

SOP from the guidelines.

AYURVEDIC APPROACH TO DRUG

RESEARCH Acharya Charaka and Acharya Bhavmishra

has been described the study of herbs and

Acharya Sharangdhar described guidelines for

drug preparation. This is not completely

followed in the present practice and most of

the drugs are combined with keeping in view

of their chemical constituent. Moreover drugs

used today are prepared from plant extracts

(mostly alcoholic). Ancient scholars used drug

as a whole and extracts used were water

extracts only. Use of whole plant is having

added benefit over its extract; the greatest

example is sarpagandha (Rauvolfia serpentina‎)

roots when used as whole plant has no adverse

drug reactions like – suicidal tendency,

bradycardia, drowsiness, etc. and controls

blood pressure. But the use of its extracted

alkaloid serpentine (reserpine) produces

adverse drug reaction similar adverse effect is

observed in sarpagandha ghanvati too.

Ayurvedic drug research is based on

pharmaceutical (bahukalpam), pharmacologica

l (bahugunam), pharmacognosical (sampanam)

and therapeutically potent (yogyam) [2]. As

discussed above a physician ought to see deha

bala, chitta bala and agni bala, Acharya

Charaka clarified this in viman 8 whilst

describing karyafala (outcome of treatment).

Acharya Charaka described that a drug is said

to be effective if it heals disease and ought to

improve complexion, physical strength and

immunity, regulate digestion & metabolism,

regular sleep and awakening i.e. it should also

improve general wellbeing of the patient [3]. It

is observed in contemporary science that drug

whilst correcting illness produce adverse drug

reaction or idiosyncrasies; some are even more

dangerous than the primary illness for instance

quinine used for treatment of malaria may

produce ITP, acute renal failure. Amodiaquine

may have agranulocytosis, Amodiaquine may

produce intravascular hemolysis over and

above gastric disturbance, headache,

irregularities, etc. The cited idiosyncrasies are

only the example and most of drug used have

such adverse effects, owing to these adverse

drug reaction FDA has proscribed various

drugs, so research in the medicine ought to be

based on approach of Acharya Charaka.

Importance of prakriti and vikriti [4] in clinical

medicine has been acknowledged in ayurvedic

medicine. Ayurvedic medicines are grouped as

vyadhi-hara, dosha-hara and ubhaya-hara.

1. Vyadhi-hara means a drug has effect on

disease i.e. corrects dosha-dushya

sammurchana (as dosha-dushya

sammurchana is the important event in

disease production) and can be used

irrespective of prakriti of individual,

doshas involved for instance most of

herbo-mineral compounds are of this

nature, vatsanabh (Aconitum ferox) in

jwara, pushkarmula (I. racemosa) in chest

pain, somalata in asthma, etc. A physician

can prescribe this medicine use these

medicines with observing only the age and

gravity of disease for dosage.

2. Dosha-hara means drug that corrects

dosha. It through medical examination –

ten fold examinationiv and analyze morbid

medical condition on doshik paradigm [5–

6]. This is used in ayurvedic practice and

needs perfection in clinical examination

minute observation is prerequisite.

3. Ubhaya-hara means these are such drugs

which not only corrects the dosha

primarily involved in disease but also

corrects dosha-dushya saamurchana, for

example use of dashmula kwath vatic

sotha (pitting edema) is vata shamak and

shothaghana (anti-inflammatory). These

drugs are combinations are appreciated as

has dual action.

This concept of ayurveda is not accepted in

previous years, but concept of individualized

care is now accepted for research purpose also.

A recent research on rheumatoid arthritis

carried out by Ramesh C. Juyal and his team

validated concept of prakriti and its


Volume 1, Issue 1

__________________________________________________________________________________________


importance in clinical efficacy of the drug. The

conclusion drawn by them clarifies this

concept they concluded that “This exploratory

study suggests discrete causal pathways for

RA etiology in prakriti based subgroups,

thereby, validating concepts of prakriti and

personalized medicine in Ayurveda.

Ayurgenomics approach holds promise for

biomarker discovery in complex diseases”[7].

SUMMARY Drug designing and drug research has been

unique approach in ayurveda and not only

objected to treat disease but to bring back

normalcy after treatment, it covers all the three

component of body. This holistic approach

reduces probabilities of adverse drug reaction

or idiosyncrasies. Research in Ayurveda ought

to be based on ayurveda principles to validate

the facts described in ayurvedic treatises.

REFERENCE

1. Achrya Charaka, Charaka Samhita,

Niryana Sagar press third edition.1941:

Ch. Ni. 8/36-37 “ ddhisth na ṣay as

th ṁ ōg ṇ mupala ṣayēt| susū ṣm mapi

ca p jñō dēh gnibalacētas m||36|| y dhy

a asth iśēṣ n hi jñ t jñ t vicakṣaṇaḥ|

tasy ṁ tasy ma asth y ṁ catuḥś ēyaḥ

p apadyatē||37||

2. Achrya Charaka, Charaka Samhita, Niryan

a Sagar press third edition.1941: Ch. Su.

9/7 ”bahut tat ayōgyat amanē a idha al

pan | sampaccēti catuṣ ō'yaṁ d a y ṇ ṁ

guṇa ucyatē||7||


Niryana Sagar press third edition. 1941:

Ch. Vi. 8/89 “ yaṁ dh tus myaṁ, tasya

la ṣaṇaṁ i ōpaśamaḥ| pa ī ṣ t asya-

ugupaśamanaṁ, s a a a ṇayōgaḥ, śa ī ōp

acayaḥ, bala ddhiḥ, abhya ah y bhil ṣa

ḥ, uci h a lē, abhya ah tasya c h asy

a kale samyagja aṇaṁ, nid l bhō yath

laṁ, ai iṇ ṁ ca s apn n mada śanaṁ,

su hēna ca p atibōdhanaṁ, tamūt apu īṣ

a ētas ṁ mu tiḥ, sa ai manōbuddhīn

d iy ṇ ṁ c y pattiriti||89||

4. Achrya Charaka, Charaka Samhita, Niryan

a Sagar press third edition 1941: Ch. Vi.

8/94 “pa ī ṣēta p a titaśca, i titaśca,

s ataśca, saṁhananataśca, p am ṇataśca,

s tmyataśca, satt ataśca, h aśa titaśca, v

y y maśa titaśca, ayastaścēti, balap am

ṇa iśēṣagrahaṇahētōḥ||94||



Ch. Vi. 8/94 “tasyōpalabdhi nid n-

apū a ūpaliṅgōpaśayasamp ptitaḥ||6||

6. Achrya Madhavakar, Madhav Nidan,


Ma. Ni. 1/4 nid naṁ pū a ūp -ṇi

ūp ṇyupaśayastath | samp ptiścēti

ijñ naṁ ōg ṇ ṁ pañcadh sm tam ||4||

7. Juyal RC, Negi S, Wakhode P, Bhat S,

Bhat B, et al. Potential of Ayurgenomics

Approach in Complex Trait Research:

Leads from a Pilot Study on Rheumatoid

Arthritis. PLoS ONE.2012; 7(9): e45752.

doi:10.1371/journal.pone.0045752.



Volume 1, Issue 1

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Synthesis and Anti-Bacterial Activity Profile of Cyclized

Diazonium Compounds

Priti Jain*, L. Naga Rajiv, Hemant R. Jadhav Department of Pharmacy, Birla Institute of Technology and Sciences, Pilani,

Rajasthan, India

Abstract Synthesis of cyclised diazonium compounds and their in vitro activity against various microorganisms is described. Several primary aromatic amines were diazotised and the

resulting diazotised compounds were coupled with active methylene compounds to give

hydrazono derivatives. These were cyclized with hydrazine hydrate, phenyl hydrazine, urea and o-phenylene diamine to give pyrazolin-5-one, substituted pyrazolin-5-ones,

pyrimidin-di-ones and benzodiazepinone derivatives, respectively. Some hydrazine

derivatives were also produced by reduction of diazo compounds with Sn/HCl. The synthesized compounds were assessed for their antimicrobial profile against Escherichia

coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas putida. Chloramphenicol and tetracycline were used as standards for the comparison of activity. Some of the

compounds were found to exhibit promising antibacterial activity.

Keywords: diazotization, pyrazolinone, pyrimidinone, benzodiazepine, antimicrobial

*Author for Correspondence E-mail: [email protected]

INTRODUCTION Heterocyclic compounds hold a special place

among pharmaceutically important natural and

synthetic materials. The remarkable ability of

heterocyclic nuclei to serve both as

biomimetics and active pharmacophores has

largely contributed to their unique value as

traditional key elements of numerous drugs.

Five or six membered ring compounds are

ranked high among various classes of organic

compounds in respect to the diverse biological

activities. Pyrazolinone is a five membered

lactam ring compound containing two

nitrogens and ketone in the same molecule.

Lactams are reported to have varying

pharmacological activity. Some pyrazolinones

are nonsteroidal anti-inflammatory agents used

in the treatment of arthritis and other

musculoskeletal and joint disorders. They also

possess activities like antibacterial, antifungal,

anti-inflammatory [1], antidiabetic, analgesic,

antipyretic, antiviral and antineoplastic activity

[2].

Pyrimidine ring structures also have received

significant attention owing to their diverse

range of biological properties. Pyrimidine

nucleus is present in compounds used

clinically such as antibacterial agents,

anticancer agent, antiviral agents, antifungal

agents and antimalarial agents. Several

important sulfonamide drugs are pyrimidine

derivatives namely sulfadiazine, sulfamerazine

and sulfadimidine. The nucleus also is an

integral part of DNA and RNA, hence serves

as an important part of nucleoside antibiotics,

antibacterials and cardiovascular agents [3– 5].

The benzodiazepine nucleus is also a well-

studied traditional pharmacophoric scaffold

that has emerged as a core structural unit of

various sedative-hypnotics, muscle relaxants,

anxiolytics, antistaminic and anticonvulsant

agents. Therefore diversely substituted

benzodiazepine nuclei can serve as synthons

for developing new drugs [6]. Keeping these

facts in mind, we synthesized pyrazolin-5-one,

substituted pyrazolin-5-ones, pyrimidin-di-

ones and benzodiazepinone derivatives for

probable antibacterial activity.

EXPERIMENTAL General:

Melting points were determined on Buchi-530

melting point apparatus and are reported

uncorrected. IR spectra were recorded on a


mailto:[email protected]

Synthesis and Anti-Bacterial Activity Profile Jain et al.


Shimadzu-Prestige-21 FTIR and NMR on

Bruker-400 MHz. All analytical samples were

observed by thin layer chromatography, which

was performed on EM Silica gel 60 F254

sheets (0.2 mm) using suitable solvent system.

The spots were detected with a model UV

lamp.

Diazotization of Primary Aromatic Amines

A mixture of aromatic amine (0.01 mole) in

concentrated HCl (5 ml) was cooled to 0 - 5oC

under ice. Cooled sodium nitrite solution (1.5

g in 10 mL of water) was added to it dropwise

over 10 minutes. Addition of the solution was

continued till the reaction mixture gives end

point when tested with starch –iodide paper.

General Procedure for the Preparation of

Hydrazono Derivatives (C)

The diazonium salt formed was then reacted

with ethyl acetoacetate, which serves as a

source of active methylene group (Figure 1).

This proton of methylene group is very active

and can replace anion from other compounds.

Other compounds like ethyl malonate, ethyl

acetone, ethyl cyanoacetate can also be used as

a source of active methylene group.

PROCEDURE To the diazotized compound, the cooled

mixture of active methylene compound formed

from ethyl acetoacetate (0.01 M) and sodium

acetate (0.05 M) in ethanol (50 ml) was added

drop-wise with stirring for about 15 minutes.

The reaction mixture was left for 2 hours at

room temperature. Recrystallization was done

using suitable solvent [7].

Preparation of Pyrazoline-5-one Derivatives

(D1-D8)

To compound ‘C1 to C8’ was added equimolar

Solution of hydrazine hydrate and 20 ml

ethanol. The mixture was then refluxed for

about 4 hours. The completion of reaction was

monitored by TLC using suitable solvent

system. The final product was recrystallised

using ethanol [8, 10].

Preparation of 2-Phenyl Pyrazole-3-one

Derivatives (E1-E8)

30mL of glacial acetic acid was added to ‘C1

to C8’ and stirred. To the resulting solution

was added equimolar quantity of phenyl

hydrazine and anhydrous sodium acetate. It

was then refluxed for about 5 hours. The

reaction mixture was poured in ice cool water

and stored in refrigerator overnight. Filtered

and recrystallized with suitable solvent [8, 10].

Preparation of Substituted 2, 4-Pyrimidine-

dione Derivatives (F1-F8)

To compound ‘C1 to C8’ was added equimolar

solution of urea and 40 ml ethanol. The

mixture was then refluxed for about 3-4 hours.

The completion of reaction was monitored by

TLC using suitable solvent system. On

completion of reaction, the mixture was cooled

under ice and kept for about one hour. The

final product was recrystallised using ethanol

[9, 10].

Preparation of Substituted Benzodiazepine

Derivatives (G1-G8)

To compounds ‘C1 to C8’ was added about 6

ml glacial acetic acid. Half molar of o-

phenylene diamine was taken and dissolved in

minimum quantity of glacial acetic acid. Both

solutions were mixed and refluxed for about 6

hours, cooled and kept overnight. It was then

filtered and recrystallized using acetic acid

[11].

Fig. 1: Reaction of Diazonium Compounds with ethylacetoacetate.


Volume 1, Issue 1


Preparation of Hydrazine Derivatives (H1-

H8)

To stannous chloride (2.1 gm), 2 ml HCl was

added and cooled. This solution was slowly

added to diazonium salt solution. It was kept

for 2-3 hours, filtered and recrystallized.

Antimicrobial Screening

The synthesized compounds were screened for

their antimicrobial activity against Escherichia

coli, Staphylococcus aureus, Bacillus cerius

and Pseudomonas putida by well plate

method. The nutrient broth was prepared by

dissolving 25 gm of Laurea Bertanni (LB)

broth in 1000 ml of distilled water in a conical

flask. 2% of agar powder was added to the

nutrient broth to prepare agar media. The

solution was autoclaved at 121°C, 15psi for 15

minutes. The broth was then inoculated with

culture as per USP guidelines and incubated

for 15-18 hours at 37°C. 2% of agar powder

was added to the nutrient broth to prepare agar

media. Agar plates were prepared and wells

were made in it for solvent, standard drug and

for different concentrations (200 µg/ ml and

150 µg/ ml) of synthesized compounds. These

were incubated at 37°C and zone of inhibition

in cm was recorded after 12 hours. The

experiments were performed in triplicate and

average of the data is recorded in table 1 and

synthesis of cyclized and reduced diazonium

compounds is shown in Figure 2.

Table 1: Activity Profile of Synthesized Compounds.

Drug code Zone of inhibition in cm

E.coli B. cerius S.aureus P. putida

Standard drug 2.5 3.0 2.5 2.0

E5 0.4 2.1 1 Inactive

C5 1.1 Inactive 0.8 Inactive

G5 Inactive 1.9 Inactive 1.8

H2 3.0 2.8 1.9 2.2

D2 Inactive Inactive Inactive Inactive

F2 Inactive 2 .0 Inactive 1.7

C2 0.3 2.5 Inactive Inactive

G2 2.1 Inactive 1.2 2.2

E2 Inactive Inactive Inactive Inactive

C3 Inactive 1.2 1.9 Inactive

H3 2.5 0.6 Inactive 1.1

C1 Inactive Inactive Inactive Inactive

D1 Inactive 1.5 Inactive Inactive

F1 Inactive 2.5 Inactive 1.8

G1 Inactive Inactive Inactive 1.6

E1 0.2 1.9 0.8 -



Fig. 2: Reaction Scheme Showing Synthesis of Cyclized and Reduced Diazonium Compounds.

Table 2: Yield and Melting Points (in degrees celcius) of Synthesized Compounds.

S. No 1 2 3 4 5 6 7 8

R H 2-OCH3 3-Cl 4-Cl 4-CH3 3-CH3 4-OCH3 3-OCH3

D %Y 95 96 64 60 15 5 47 5

MP 180 215 200 180 187 - 178 -

E %Y 91 97 17 5 80 43 25 95

MP 120 132 170 5 148 152 121 153

F %Y 92 97 26 67 72.5 5 60 5

MP 142 101 160 162 77 - 65 -

G %Y 90 15 62.5 22.3 57 70 5 82.7

MP 127 123 - 110 98 85 - -

H %Y 75 92 95 51 72 94.8 90 92

MP 120 160 180 - 120 120 178 151


Volume 1, Issue 1


RESULTS AND DISCUSSION All compounds synthesized were characterized

using melting point, infrared, 1H-NMR and

mass spectroscopy.The yield and melting point

of all the compounds is reported in table 2.

D1:5-Methyl-4-(phenyl-hydrazono)-2,4-

dihydro-pyrazole-3-one:

IR data: 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1

(Aromatic C-H stretching),

1650-1690 cm-1

(C=O stretching), 1600-1700

cm-1

(C=N stretching), 1580-1450 cm-1

(C=C

stretching) NMR: 0.9δ (CH3), 6.2-7.0δ5

(Aromatic protons), 5.6 δ (N-H protons),

m/z:201.31

D2:4-[(2-methoxy-phenyl)-hydrazono]5-

methyl-2,4-dihydro-pyrazole-3-one:

IR data: 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1


2818 (C-H stretching of CH3), 1650-1690 cm-

1 (C=O stretching), 1600-1700 cm

-1 (C=N

stretching), 1580-1450 cm-1

(C=C stretching),

1150 cm-1 (C-O stretching), m/z:232.13

NMR: 0.9δ (CH3), 6.3-6.5 δ (Aromatic

protons), 6 δ (N-H protons), 3.73δ (OCH3)

D3:4-[3-Chloro-phenyl)-hydrazono]5-


IR data: 3380-3400 cm-1

(N-H stretching),

2950-3120 cm-1


1650-1690 cm-1


cm-1


(C=C

stretching) NMR: 0.9 δ (CH3), 6.3-6.7 δ

(aromatic protons), 6δ (N-H protons), m/z

236.08

D4:4-[4-Chloro-phenyl)-hydrazono]5-


IR data: 3380-3400 cm-1

(N-H stretching),

2950-3120 cm-1


1650-1690 cm-1


cm-1


(C=C

stretching) NMR: 0.9δ (CH3), 6.4-7.2 δ

(aromatic protons), 6.2 δ (N-H protons), m/z

236.08

D5:4-[4-methyl-phenyl)-hydrazono]5-

methyl-2,4-dihydro-pyrazole-3-one: IR data: 3380-3400 cm

-1 (N-H stretching),

2950-3120 cm-1


2750 cm-1

(C-H stretching), 1650-1690 cm-1

(C=O stretching), 1600-1700 cm-1

(C=N


(C=C stretching)

NMR:0.9 δ (CH3), 2.34 δ (CH3 of phenyl),

6.3-6.8δ (aromatic protons), 6δ (N-H protons),

m/z 216.13

D6:4-[3-Chloro-pheny)l-hydrazono]5-


IR data: 3380-3400 cm-1

(N-H stretching),

2950-3120 cm-1


1650-1690 cm-1


cm-1


(C=C

stretching) NMR: 0.9δ (CH3), 2.34 δ (CH3 of

phenyl), 6.2-6.8δ (aromatic protons), 6 δ (N-H

protons)

D7:4-[4-methoxy-pheny)l-hydrazono]5-


IR data: : 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1




-1 (C=N


(C=C stretching),

1150 cm-1 (C-O stretching) NMR: 0.9δ

(CH3), 3.78 δ (OCH3 of phenyl), 6.2-6.8δ

(aromatic protons), 6δ (N-H protons),

m/z:232.13

D8:4-[3-methoxy-pheny)l-hydrazono]5-


IR data: : 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1




-1 (C=N


(C=C stretching),

1150 cm-1 (C-O stretching) NMR: 0.9 δ

(CH3), 3.75δ (OCH3 of phenyl), 6.2-6.8δ

(aromatic protons), 5.6 δ (N-H protons),

m/z:232.13

E1: 5-methyl-2-phenyl-4[phenyl-

hydrazono]- 2,4-dihydro-pyrazole-3-one:

IR data: 3458 cm-1

(N-H stretching), 2900-

3100 cm-1

(Aromatic C-H stretching), 1670-

1690 cm-1



(C=C

stretching). NMR: 0.9δ (CH3 protons)6.2-6.8,

7.0-7.3 δ (Aromatic protons), 6.8δ (NH)

E2:4[(2-methoxy-phenyl)-hydrazono]- 5-

methyl-2-phenyl-2,4-dihydro-pyrazole-3-

one:

IR data: 3345 cm-1


3100 cm-1


1690 cm-1





(C=C

stretching), 1150 cm-1

(C-O stretching) NMR:

0.9 δ (CH3 protons), 3.73δ (OCH3), 6.2-6.5,

7.0-7.6δ (Aromatic protons), 6.9δ (NH),

m/z=308.13

E3:4-[3-chloro-phenyl)-hydrazono]-5-


one:

IR data: 3455 cm-1


3120 cm-1


1690 cm-1



(C=C

stretching), NMR: 0.9δ (CH3 protons), 6.2-

6.5, 7.0-7.6δ (Aromatic protons), 7.0δ (NH),

m/z=312.08

E4:4-[(4-chloro-phenyl)-hydrazono]- 5-


one:

IR data: 3455 cm-1


3120 cm-1


1690 cm-1



(C=C

stretching) NMR: 0.9 δ (CH3 protons), 3.73δ

(OCH3),6.2-6.5, 7.0-7.6 δ (Aromatic protons),

6.8δ (NH), m/z=312.08

E5: 5-methyl-2-phenyl-4[p-tolyl-

hydrazono]-2, 4-dihydro-pyrazole-3-one:

IR data: 3425 cm-1


3320 cm-1


1690 cm-1



(C=C

stretching), 2850 cm-

(C-H stretching) NMR:

0.9, 2.35δ (CH3 protons), 6.3-6.81, 7.0-7.64δ

(Aromatic protons), 6.8δ (NH), m/z=292.13

E6:5-methyl-2-phenyl-4[m-tolyl-

hydrazono]-2,4-dihydro-pyrazole-3-one:

IR data: 3425 cm-1


3320 cm-1


1690 cm-1



(C=C

stretching), 2850 cm-

(C-H stretching) NMR:

0.9,2.35δ (CH3 protons)6.2-6.8, 7.0-7. δ3

(Aromatic protons), 6.8δ (NH), m/z=292.13

E7:4[(4-methoxy-phenyl)-hydrazono]-5-


one:

IR data: 3345 cm-1


3100 cm-1


1690 cm-1



(C=C



0.9δ (CH3 protons), 3.73 δ (OCH3),6.2-6.5,

7.0-7.6δ (Aromatic protons), 6.8 δ (NH),

m/z=308.13

E8:4[(3-methoxy-phenyl)-hydrazono]-5-


one:

IR data: 3345 cm-1


3100 cm-1


1690 cm-1



(C=C



0.9δ (CH3 protons), 3.73δ (OCH3),6.2-6.5,

7.0-7.6δ (Aromatic protons), 6.84δ (NH),

m/z=308.13

F1:6-methyl-5(phenyl-hydrazono)-5-H-

pyridine-2, 4-dione:

IR data: 3424 cm-1 (N-H stretching), 3052

cm-1 (Aromatic C-H stretching), 2800- 2900

cm-1 (aliphatic C-H stretching), 1688, 1676

cm-1 (C=O stretching), 1592 cm-

1, 1565 cm-

1,

1481 cm-1 (C=N, C=C stretching), 1284 cm-

1

(N-N=C stretching) NMR: 0.9δ (CH3), 7, 10 δ

(NH protons), 6.4-7.01δ (Aromatic protons),

m/z=230.22

F2:5[(2-methoxy-phenyl)-hydrazono]-6-

methyl-5-H-pyridine-2, 4-dione:





1, 1565 cm-

1,


1

(N-N=C stretching), 1243 cm-1

(C-O

stretching) NMR: 0.9 (CH3), 7, 10(NH

protons), 6.3-6.51 (Aromatic protons), 3.5

(methoxy protons), m/z=260.09

F3:5[(3-chloro-phenyl)-hydrazono]-6-


IR data: 3345 cm-1 (N-H stretching), 3153 cm-

1 (Aromatic C-H stretching), 2800- 2900 cm-

1

(aliphatic C-H stretching), 1688, 1676 cm-1

(C=O stretching), 1592 cm-1, 1565 cm-

1, 1481

cm-1 (C=N, C=C stretching), 1284 cm-

1 (N-

N=C stretching) NMR: 0.9δ (CH3), 7.1, 10.2δ

(NH protons), 6.3-6.6 δ (Aromatic protons),

m/z=264.04


Volume 1, Issue 1


F4:5[(4-chloro-phenyl)-hydrazono]-6-




1



1, 1481


1 (N-

N=C stretching) NMR: 0.9δ (CH3), 7, 10 δ


m/z=264.04

F5:6-methyl-5-(p-tolyl-hydrazano)-5-H-




1



1, 1481


1 (N-

N=C stretching) NMR: 0.9, 2.3δ (CH3), 7, 10

δ (NH protons), 6.3-6.6δ (Aromatic protons),

m/z=244.10

F6:6-methyl-5-(m-tolyl-hydrazano)-5-H-




1



1, 1481


1 (N-

N=C stretching) NMR: 0.9, 2.3δ (CH3), 7, 10

δ (NH protons), 6.3-6.6δ (Aromatic protons),

m/z=244.10







1, 1565 cm-

1,


1


(C-O

stretching) NMR: 0.9δ (CH3), 7, 10 δ (NH

protons), 6.3-6.51δ (Aromatic protons), 3.5δ








1, 1565 cm-

1,


1


(C-O

stretching) NMR: 0.9δ (CH3), 7, 10δ (NH

protons), 6.3-6.51δ (Aromatic protons), 3.5δ


G1:4-methyl-3(-phenyl-hydrazono)-1,3-

dihydro-benzo-1,4-diazepin-2-one:

IR data: 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1




-1 (C=N


(C=C stretching)

NMR: 0.9δ (CH3), 3.1δ (CH2), 4, 7δ (NH

protons), 6.4-7.01δ (Aromatic protons),

m/z=264.14

G2:3[(2-methoxy-phenyl)-hydrazono]-4-

methyl-,3-dihydro-benzo-1,4-diazepin-2-

one:

IR data: 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1




-1 (C=N


(C=C stretching),

1280 cm-1

(C-O stretching) NMR: 0.9δ (CH3),

3,2 δ (CH2), 3.9δ (methoxy protons), 4, 7δ


m/z=308.13

G3:3[(3-chloro-phenyl)-hydrazono]-4-


one:





1, 1565 cm-

1,


1

(N-N=C stretching) NMR: 0.9δ (CH3), 3,2 δ

(CH2), 3.9 δ (methoxy protons), 4, 7 δ (NH

protons), 6.4-8δ (Aromatic protons),

m/z=312.08

G4:3[(4-chloro-phenyl)-hydrazono]-4-


one:





1, 1565 cm-

1,


1

(N-N=C stretching) NMR: 0.9δ (CH3), 3,2δ

(CH2), 3.9δ (methoxy protons), 4, 7 δ (NH



protons), 6.4-8δ (Aromatic protons),

m/z=312.08

G5:4-methyl-3(-p-tolyl-hydrazono)-1,3-




1



1, 1481


1 (N-

N=C stretching) NMR: 0.9 , 2.35 δ (CH3),

3.2δ (CH2), 3.9 δ (methoxy protons), 4, 8δ

(NH protons), 6.4-7.6 δ (Aromatic protons),

m/z=292.13

G6:4-methyl-3(-m-tolyl-hydrazono)-1,3-




1



1, 1481


1 (N-

N=C stretching) NMR: 0.9 , 2.35δ (CH3), 3.2δ

(CH2), 3.9δ (methoxy protons), 3.8, 7.5 δ


m/z=292.13



one: IR data: 3400-3600 cm-1

(N-H


(Aromatic C-H

stretching), 2818 (C-H stretching of CH3),

1650-1690 cm-1


cm-1


(C=C



0.9δ (CH3), 3,2δ (CH2), 3.9δ (methoxy

protons), 4, 8δ (NH protons), 6.4-7.6δ

(Aromatic protons), m/z=308.13



one:

IR data: 3400-3600 cm-1

(N-H stretching),

2900-3100 cm-1




-1 (C=N


(C=C stretching),

1280 cm-1

(C-O stretching) NMR :0.9δ (CH3),

3.2δ (CH2), 3.9δ (methoxy protons), 4, 8 δ


m/z=308.13

H1:phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H

stretching), 3400-3500cm-1

(N-H stretching),

NMR: 2,4 δ (NH2, NH proton), 6.6-7.18δ

(Aromatic protons), m/z : 108.07

H2:2-methoxy phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H


(N-H stretching),

2856 cm-1

(C-H stretching of methoxy), 1150

cm-1

(C-O stretching) NMR: 2,4 δ (NH2, NH

proton), 3.5 δ (methoxy protons), 6.8-7.38δ


H3:3-chloro-phenyl hydrazine:

IR data: 3000-3240 cm-1

(aromatic C-H


(N-H stretching)

NMR: 2.3,4.1 δ (NH2, NH proton), 6.6-7.18δ


H4:4- chloro-phenyl hydrazine:

IR data: 3000-3240 cm-1

(aromatic C-H


(N-H stretching)

NMR: 2.3,4.1 δ (NH2, NH proton), 6.6-7.18δ


H5:4-methyl-phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H


(N-H stretching),

2856 cm-1

(C-H stretching of methyl)

NMR: 2.6,4 δ (NH2, NH proton), 2.35 δ

(methyl protons), 6.7-7.58δ (Aromatic

protons), m/z : 122.17

H6:3- methyl-phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H


(N-H stretching),

2856 cm-1

(C-H stretching of methyl)

NMR: 2,4 δ (NH2, NH proton), 2.35 δ

(methyl protons), 6.6-7.18δ (Aromatic


H7:4-methoxy phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H


(N-H stretching),

2856 cm-1


cm-1

(C-O stretching)


(methoxy protons), 6.6-7.18δ (Aromatic


H8: 3-methoxy phenyl hydrazine:

IR data: 3000-3100 cm-1

(aromatic C-H


(N-H stretching),


Volume 1, Issue 1


2856 cm-1


cm-1

(C-O stretching)


(methoxy protons), 6.6-7.18δ (Aromatic


CONCLUSION Various cyclized diazonium compounds were

synthesized possessing different heterocyclic

ring systems in good yield. The well plate

method for antibacterial activity showed

significant reduction in bacterial growth in

terms of zone of inhibition around the well.

Chloramphenicol and tetracycline were used

as standard drugs for the comparison. It was

observed that phenyl group bearing no

substituent, was inactive against E.coli and S.

aureus. Benzodiazepine derivatives and

reduced compounds displayed comparable

activity to standard against all tested strains of

micro-organisms.

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http://www.ijpsonline.com/searchresult.asp?search=&author=M+Amir&journal=Y&but_search=Search&entries=10&pg=1&s=0

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RRJoDDD (2014)© STM Journals 2014. All Rights Reserved


Volume 1, Issue 1

www.stmjournals.com

Targeting Cancer through Angiogenesis Inhibition:

Prospective of Azole Based Small Molecules

Pratap Chandra Acharya* Department of Pharmaceutical Chemistry, SPPSPTM, SVKM'S

NMIMS University, Mumbai, India

Abstract Anticancer drug discovery is a major focus area in the pharmaceutical industry and obtaining targeted drug molecules for the malignant tissue is a major hurdle in this

process. With the advancement in the knowledge of biological targets, cancer specific

molecules such as monoclonal antibodies have been designed and produced in the recent past. However, the cost and effectiveness of these special products are the biggest

challenges for cancer treatment. Small molecules are considered as the best

chemotherapeutic intervention to treat cancer at the present time. This article describes the possibility of azole based small molecules as inhibitor of tumor angiogenesis, which

can be explored for anticancer drug discovery.

Keywords: Angiogenesis, Anticancer Drugs, Monoclonal Antibodies, Azoles, Small

Molecules, HUVEC Assay


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