Bioorganic & Medicinal Chemistry Volume 21, Issue 5, 2013

ContentsPublisher’s Note pp 1041–1042

ARTICLES

Alkaloids from Sri Lankan curry-leaf (Murraya koenigii) display melanogenesis inhibitory activity: Structures ofkarapinchamines A and B

pp 1043–1049

Seikou Nakamura, Souichi Nakashima, Yoshimi Oda, Nami Yokota, Katsuyoshi Fujimoto, Takahiro Matsumoto, Tomoe Ohta,Keiko Ogawa, Sayuri Maeda, Shino Nishida, Hisashi Matsuda, Masayuki Yoshikawa*

Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thioureaskeleton as anticancer agents

pp 1050–1063

Wen Yang, Yang Hu, Yu-Shun Yang, Fei Zhang, Yan-Bin Zhang, Xiao-Liang Wang, Jian-Feng Tang, Wei-Qing Zhong*,Hai-Liang Zhu*

Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesteraseinhibitors

pp 1064–1073

Da-Hua Shi, Wei Huang, Chao Li, Ling-Ting Wang, Shi-Fan Wang*

OH OHO

O

NCl

The novel aloe-emodin derivatives, which could interact with both the CAS and PAS of AChE, possessed the better AChE-inhibition activity than tacrine(IC50 = 0.09 lM, the IC50 of tacrine is 0.26).

Bioorganic & Medicinal Chemistry 21 (2013) 1031–1040

Contents lists available at SciVerse ScienceDirect

Bioorganic & Medicinal Chemistry

journal homepage: www.elsevier .com/locate /bmc

Whole-body imaging of tumor cells by azaelectrocyclization: Visualization of metastasis dependence on glycanstructure

pp 1074–1077

Katsunori Tanaka*, Kenta Moriwaki, Satomi Yokoi, Koichi Koyama, Eiji Miyoshi, Koichi Fukase*

New PAH derivatives functionalized by cyclic nitrone framework: Synthetic design, anti-proliferative activity andinteraction with DNA

pp 1078–1081

Marian Buchlovic, Zdenek Kríz, Ctirad Hofr, Milan Potácek*

Antiparkinsonian activity of some 9-N-, O-, S- and C-derivatives of 3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol pp 1082–1087

Oleg V. Ardashov, Alla V. Pavlova, Dina V. Korchagina, Konstantin P. Volcho*, Tat’yana G. Tolstikova,Nariman F. Salakhutdinov

OH

OH N

O

ON O N

H

OH

OH

X

OH

OH

Substituent

highantiparkinsonian

activity in vivoin mice model

Substituent

decreasing or lost of antiparkinsonianactivity

OH NH2

retention of high antiparkinsonian activity

X = CH2or S

NH

N

Incorporation of b-amino acids into dihydrofolate reductase by ribosomes having modifications in thepeptidyltransferase center

pp 1088–1096

Rumit Maini, Dan T. Nguyen, Shengxi Chen, Larisa M. Dedkova, Sandipan Roy Chowdhury, Rafael Alcala-Torano,Sidney M. Hecht*

ModifiedDHFR

(2) deprotection

in vitrotranslation

COH

ACC

beta-amino acid

AUC

CUA

pET28b(+)-DHFR(TAG)

T7promoter

in vitro

transcriptionUAGmRNA

TAG

(1) pdCpA-beta-amino acid,

T4 RNA ligaseS-30 with

modified ribosome

beta-aminoacid

1032 Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040

Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a carbamoyllinker

pp 1097–1108

Kamil Kokosza, Jan Balzarini, Dorota G. Piotrowska*

N ON(EtO)2(O)P

O

NH

O

R = F, Br, Cl, Me, OMe, OEt, CN, NO2, C(O)CH3

R

NH

O

+(EtO)2(O)P

trans:cis = 90:10 to 75:25

R

Identification of small-molecule inhibitors of the human S100B–p53 interaction and evaluation of their activity inhuman melanoma cells

pp 1109–1115

Chihoko Yoshimura, Takamitsu Miyafusa, Kouhei Tsumoto*

Evolvosides C–E, flavonol-4-O-triglycosides from Evolvulus alsinoides and their anti-stress activity pp 1116–1122

Prasoon Gupta*, Upasana Sharma, Praveen Gupta, Kiran Babu Siripurapu, Rakesh Maurya

OR 1O

O R2

OH

OR 3

O1: R 1 = R2 =H2; R 1 = Me, R 2 = H3: R 1 = R2 = Me

R3 = β-D -g lucopyranoside -(1 -2 )-α -L -rhamnopyranosyl-(1 -6)-β-D-glucopyranoside

Secondary amines containing one aromatic nitro group: Preparation, nitrosation, sustained nitric oxide release, and thesynergistic effects of released nitric oxide and an arginase inhibitor on vascular smooth muscle cell proliferation

pp 1123–1135

Brandon Curtis, Thomas J. Payne, David E. Ash,Dillip K. Mohanty*

X

Y

ZNO2

+H2N

nn = 5 - 9

A. 2,4 - IsomerX = FY = FZ = H

B. 2,6 - IsomerX = FY = HZ = F

K2CO3DMAC

TolueneHeat

NO2HN

n

HNn

A. 2,4 - Isomer

NO2HN

n

B. 2,6 - Isomer

NHn

NO2

A'. 2,4 - Isomer

NO2

B'. 2,6 - Isomer

Nn

NO

Nn

NO

Nn

NO

Nn

ONNaNO2

THFGlacial AcOH

Secondary amines prepared from the reactions of linear aliphaticamines and 2,4-difluoronitrobenzene or 2,6-difluronitrobenzene at lowtemperatures were nitrosated. These nitric oxide donors release nitricoxide in a slow, sustained and rate-tunable manner. The released nitricoxide inhibited proliferations of aortic smooth muscle cells. Thesecondary amines were not cytotoxic towards human aortic smoothmuscle cells. Addition of ABH, an arginase inhibitor, along with theprepared NO-donors, exhibited synergistic effects in inhibiting cellproliferations.

Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040 1033

Towards new boron carriers for boron neutron capture therapy: Metallacarboranes bearing cobalt, iron and chromiumand their cholesterol conjugates

pp 1136–1142

Magdalena Białek-Pietras, Agnieszka B. Olejniczak, Shoji Tachikawa, Hiroyuki Nakamura*, Zbigniew J. Lesnikowski*

SOOR

= BH, = CH

MHH

R1 = R2 =3a: R = R1

3b: R = R2, M = Co3c: R = R2, M = Fe3d: R = R2, M = Cr

Synthesis and evaluation as potential anticancer agents of novel tetracyclic indenoquinoline derivatives pp 1143–1149

Shubhashis Chakrabarty, Michael S. Croft, Melissa G. Marko, Guillermo Moyna*

O

N

RO

MeO

MeO

CO2MeOHO

MeO

MeO

OMe R = Alkyl, Aryl

GI50 (HeLa): 6 nM - 0.3 μMGI50 (MCF-7): 2 nM - 0.04 μMGI50 (A-549): 5 nM - 0.1 μM

N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase pp 1150–1158

Mikhail S. Novikov, Vladimir T. Valuev-Elliston, Denis A. Babkov, Maria P. Paramonova, Alexander V. Ivanov,Sergey A Gavryushov, Anastasia L. Khandazhinskaya, Sergey N. Kochetkov, Christophe Pannecouque,Graciela Andrei, Robert Snoeck, Jan Balzarini, Katherine L. Seley-Radtke*

Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors pp 1159–1165

Minoru Tanaka, Xin Li, Hidemasa Hikawa, Takafumi Suzuki, Katsuhiko Tsutsumi, Masashi Sato, Osamu Takikawa,Hideharu Suzuki, Yuusaku Yokoyama*

NH

NH

NN

OMe

S

H

MeR

R = Ph, Br, Cl (11a-h, 12a-d)MTH-Trp (2) 6a-c

NH

NO Me

S

NH

e

f

g

N

NH

Me

MeO

S

1034 Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040

Mechanistic studies of the inactivation of tyrosinase by resorcinol pp 1166–1173

Michael R.L. Stratford, Christopher A. Ramsden*, Patrick A. Riley

O

OCu2+Cu2+

-

-N NN N

N N

oxy-tyrosinaseO O

H2O

Cu0Cu1+

N N

N NN N

inactivated tyrosinase

HO

reductive Cu0

OH

Oelimination

Polyamino geranic derivatives as new chemosensitizers to combat antibiotic resistant Gram-negative bacteria pp 1174–1179

Jean Michel Brunel*, Aurélie Lieutaud, Vincent Lome, Jean-Marie Pagès, Jean-Michel Bolla

NH

ROO

OHR NH2+

BOP (1 equiv.)

CH2Cl2, 20°C

EtN(iPr)2 (1 equiv.)

1 equiv. 1 equiv.Yields varying from 48 to83%

12 derivatives

Decrease of chloramphenicol and nalidixic acid resistance in the presence of these derivatives against MDR Gram-negative strains by 4- to 64-fold.

Synthesis of 5,7-disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as microtubule inhibitors pp 1180–1189

Aleem Gangjee*, Sonali Kurup, Charles D. Smith

N

N

CH3

NH2N

X

R15-18

R2

Anticonvulsant evaluation of aminoalkanol derivatives of 2- and 4-methylxanthone pp 1190–1198

Natalia Szkaradek*, Agnieszka Gunia, Anna M. Waszkielewicz, Lucyna Antkiewicz-Michaluk, Marek Cegła, Edward Szneler,Henryk Marona

O

O

Brtoluene/K2CO3

8

7

6

5 O 4

3

2

1

O

NR

R'R'' R''

aminolysis

R = 1-aminopropan-2-ol, 2-aminopropan-1-ol, 2-amino-2-methylpropan-1-ol, 2-aminobutan-1-olR' = H, CH3R" = Cl, OCH3

ED50 from 47.57 mg/kg (PI 8.41)

Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040 1035

9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: Optimized preparation,including identification of by-products formed, and antiviral evaluation in vitro

pp 1199–1208

Marcela Krecmerová*, Petr Jansa, Martin Dracínsky, Petra Sázelová, Václav Kašicka, Johan Neyts, Joeri Auwerx,Eleonóra Kiss, Nesya Goris, George Stepan, Zlatko Janeba

Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in aMixed Lymphocyte Reaction assay

pp 1209–1218

Alessandro Stella, Kristien Van Belle, Steven De Jonghe, Thierry Louat, Jean Herman, Jef Rozenski, Mark Waer,Piet Herdewijn*

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatmentof diabetic macular edema

pp 1219–1233

Takayuki Inoue*, Masataka Morita, Takashi Tojo, Kousei Yoshihara, Akira Nagashima, Ayako Moritomo, Mitsuru Ohkubo,Hiroshi Miyake

10

HNNH2N

HO

HNS

N

The thiazole derivative 10 is a potent and selective VAP-1 inhibitor.

The effect of absolute configuration on activity, subtype selectivity (M3/M2) of 3a-acyloxy-6b-acetoxyltropanederivatives as muscarinic M3 receptor antagonists

pp 1234–1239

Zhi-Peng Wang, Hui-Zhong Liu, Liang Zhu, You-Min Hu, Yong-Yao Cui,Yin-Yao Niu*, Yang Lu, Hong-Zhuan Chen

All pharmalogical results implied that the absolute configuration of 3a-acyloxy-6b-acetoxyltropanederivatives played an important role in muscarinic M3 antagonistic activity and subtype selectivity(M3/M2).

1036 Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040

Selection of heptapeptides that bind helix 69 of bacterial 23S ribosomal RNA pp 1240–1247

Moninderpal Kaur, Chamila N. Rupasinghe, Edvin Klosi, Mark R. Spaller, Christine S. Chow*

Synthesis and mechanistic studies of novel spin-labeled combretastatin derivatives as potential antineoplastic agents pp 1248–1256

Ying-Qian Liu*, Xiao-Jing Li, Chun-Yan Zhao, Xiang Nan, Jing Tian, Susan L. Morris-Natschke, Zhi-Jun Zhang,Xiao-Ming Yang, Liu Yang, Lin-Hai Li, Xing-Wen Zhou, Kuo-Hsiung Lee*

MeO

MeOOMe

OMeNH2

MeO

MeOOMe

OMeNH R

O

14a-d

R=NO

NO

NO

NO

a b c d

a R=Hb R=Mec R=CHMe2d R=(CH2)2SCH3

e R=CH(Me)CH2Mef R=Prolineg R=CH2Ph

MeO

MeOOMe

OMeNH

HN

R

OO N O

O21a-h

NH

H2Ch R=

3 (AVE8063)

Design, synthesis and structure–activity relationship of novel tricyclic benzimidazolone derivatives as potent 18 kDatranslocator protein (TSPO) ligands

pp 1257–1267

Takayuki Fukaya*, Toru Kodo, Takeo Ishiyama, Hiroyuki Nishikawa, Satoko Baba, Shuji Masumoto

N

NO

NR1R2

O

X

O

NO

O

NMe

6TSPO Ki = 1.6 nM

N

N

N

O

O

X

27 (X = Ph)

41 (X = m-MeO-Ph)

48 (X = 3-PyNH)

TSPO Ki = 0.94 nM

TSPO Ki = 0.11 nM

TSPO Ki = 2.0 nM

We obtained dihydroimidazoquinolinone derivatives with potent affinity for TSPO (subnanomolar Ki values), by conversion of the benzoxazolone skeleton to atricyclic benzimidazolone ring. Further optimization of these compounds led to compound 48 with potent affinity for TSPO and good in vitro PK profile.

Retrospective group fusion similarity search based on eROCE evaluation metric pp 1268–1278

Sorin I. Avram, Luminita Crisan, Alina Bora, Liliana M. Pacureanu, Stefana Avram, Ludovic Kurunczi*

Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040 1037

Nebulosides A–B, novel triterpene saponins from under-ground parts of Gypsophila arrostii Guss. var. nebulosa pp 1279–1283

Idris Arslan*, Ali Celik, Matthias F. Melzig

O

OHOH

O

O

O

O

O

O O

OOH

OH OH

OOH

O

OH

OHOH

OH

CHO

OH

O

O

OH O

OHO

OHO

O

OH

OH

OH

OH

OH

O

OHOH

OH

0

20

40

60

80

100

120

140

Neb A Neb B Neb A + S Neb B + S S

Viab

ility

(%)

Nebuloside A and B novel triterpene saponins from Gypsophila arrostii var.nebulosa showed cytotoxicity enhancing property on saporin a type-I ribosomeinactivating protein.

Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene4-substituents

pp 1284–1304

Dan Niculescu-Duvaz, Ion Niculescu-Duvaz, Bart M. J. M. Suijkerbuijk, Delphine Ménard, Alfonso Zambon, Lawrence Davies,Jean-Francois Pons, Steven Whittaker, Richard Marais, Caroline J. Springer*

R-1i BRAF IC50=0.191 uM

N

HN

N

O NS

CF3HO

1q BRAF IC50=0.009 uM

N

HN

N

O N

OH

Selective inhibition of glycosyltransferases by bivalent imidazolium salts pp 1305–1311

Yin Gao, Jason Z. Vlahakis, Walter A. Szarek*, Inka Brockhausen*

N NnNN

Bis-imidazolium salts

H3C CH3

2Cl

n = 4, 6, 8, 10−16, 18, 20, 22

Bis-imidazolium salts have been synthesized and are the first of their type showing selective inhibitory activity towards glycosyltransferases.

N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, cellular receptor tyrosine kinase inhibitory activities andin vivo evaluation as antiangiogenic, antimetastatic and antitumor agents

pp 1312–1323

Aleem Gangjee*, Ojas A. Namjoshi, Jianming Yu, Michael A. Ihnat,Jessica E. Thorpe, Lora C. Bailey-Downs

1038 Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040

Naphthalenyl derivatives for hitting P-gp/MRP1/BCRP transporters pp 1324–1332

Nicola A. Colabufo*, Marialessandra Contino, Mariangela Cantore, Elena Capparelli, Maria Grazia Perrone,Giuseppe Cassano, Giuseppe Gasparre, Marcello Leopoldo, Francesco Berardi, Roberto Perrone

N

Y

N

O

O

R

O

N

O

O

R

R = H, OH, OCH3, Br, F

Y = O, S

Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase pp 1333–1343

Huiying Li, Fengtian Xue, James M. Kraus II, Haitao Ji, Kristin Jansen Labby, Jan Mataka, Silvia L. Delker, Pavel Martásek,Linda J. Roman, Thomas L. Poulos*, Richard B. Silverman*

Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: Synthesis, crystallography, modeling,kinetic and cellular based studies

pp 1344–1348

Peter Šilhár, Nicholas R. Silvaggi, Sabine Pellett, Katerina Capková, Eric A. Johnson, Karen N. Allen, Kim D. Janda*

NH

OOH

3a, Ki = 460 nM

NH

OOH

XKi ~ 30 nM

Synthesis and biological evaluation of novel 2,4-disubstituted quinazoline analogues as GPR119 agonists pp 1349–1356

Tuan-Anh N. Pham, Zunhua Yang, Yuanying Fang, Jun Luo, Jongkook Lee, Haeil Park*

N

NO

ONH

R

H3CO2S F

R

N Boc

NH

N Boc

HN

12a 12c 12g

human GPR119 agonistsEC50 = 1 μM

N

NBoc

Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040 1039

Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4 pp 1357–1366

Nancy Ty, Renée Pontikis*, Guy G. Chabot*, Emmanuelle Devillers, Lionel Quentin, Stéphane Bourg, Jean-Claude Florent*

OTHER CONTENTS

Corrigendum p 1367

Available online at www.sciencedirect.com

Indexed/Abstracted in: Beilstein, Biochemistry & Biophysics Citation Index, CANCERLIT, Chemical Abstracts, ChemistryCitation Index, Current Awareness in Biological Sciences/BIOBASE, Current Contents: Life Sciences, EMBASE/ExcerptaMedica, MEDLINE, PASCAL, Research Alert, Science Citation Index, SciSearch, TOXFILE. Also covered in the abstract and citationdatabase SciVerse Scopus�. Full text available on SciVerse ScienceDirect�

ISSN 0968-0896

*Corresponding authorSupplementary data available via SciVerse ScienceDirect

COVER

PAH coupled to cyclic nitrones entered into interaction with DNA duplex, its docking was modelled and action tested for antiproliferativeactivity against tumor cells [Buchlovic, M.; Kríz, Z.; Hofr, C.; Potácek, M. Bioorg. Med. Chem. 2013, 21, 1076–1079.]

1040 Contents / Bioorg. Med. Chem. 21 (2013) 1031–1040