Bioorganic & Medicinal Chemistry Volume 22, Issue 6, 2014

Contents

ARTICLES

Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat model of neuropathic pain: Amechanism dependent on CaV2.2 channel inhibition

pp 1797–1803

Grigoris Zoidis*, Alejandro Sandoval, Jorge Baruch Pineda-Farias, Vinicio Granados-Soto, Ricardo Felix*

Here, we report the synthesis of a GABA analog, GZ4 with structure–activityrelationship to gabapentin, a widely used drug in the treatment of chronicpain. By using a combined approach of spinal nerve ligation-inducedneuropathic pain model as well as electrophysiological recordings andmolecular biology, we disclose some relevant aspects on the mechanism ofaction of this novel gabapentinoid drug.

Interaction kinetics of liposome-incorporated unsaturated fatty acids with fatty acid-binding protein 3 by surfaceplasmon resonance

pp 1804–1808

Maria Carmen Tan, Shigeru Matsuoka, Hikaru Ano, Hanako Ishida, Mika Hirose, Fuminori Sato, Shigeru Sugiyama,Michio Murata*

Polyphenols bearing cinnamaldehyde scaffold showing cell growth inhibitory effects on the cisplatin-resistantA2780/Cis ovarian cancer cells

pp 1809–1820

Soon Young Shin, Hyeryoung Jung, Seunghyun Ahn, Doseok Hwang, Hyuk Yoon, Jiye Hyun, Yeonjoong Yong, Hi Jae Cho,Dongsoo Koh, Young Han Lee, Yoongho Lim*

Bioorganic & Medicinal Chemistry 22 (2014) 1791–1796

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Bioorganic & Medicinal Chemistry

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

Design, synthesis and evaluation of N-substituted saccharin derivatives as selective inhibitors of tumor-associatedcarbonic anhydrase XII

pp 1821–1831

Melissa D’Ascenzio, Simone Carradori*, Celeste De Monte, Daniela Secci, Mariangela Ceruso, Claudiu T. Supuran*

NHS

O

O OX R

DMF, 80°CN

S

O

O OK2CO3 R

X = Cl, Br

Potent and Selective Inhibitors of the cancer relatedisoform of Carbonic Anhydrase: CAXII

up to 89% yield

Saccharin

NS

O

O OOEt

O

K i CA XII = 76.5 nM

K i CA I/K i CA XII > 653K i CA II/Ki CA XII = 29

NS

O

O OOH

O

K i CA XII = 41.9 nM

K i CA I/K i CA XII > 1193K i CA II/Ki CA XII > 1193

Stereoselective preparation of pyridoxal 1,2,3,4-tetrahydro-b-carboline derivatives and the influence of their absoluteand relative configuration on the proliferation of the malaria parasite Plasmodium falciparum

pp 1832–1837

Renate Brokamp, Bärbel Bergmann, Ingrid B. Müller, Stefan Bienz*

NH

NH2

CO2Me

N Me

OHHO

D orL

H O

NH

NH

CO2Me

N Me

OHHO

cis-L1trans-L1

MS 3Å

CH2Cl2

antiplasmodial activity

cis-D1trans-D1

D orL

Evaluation of 1,2,5-thiadiazoles as modulators of M1/M5 muscarinic receptor subtypes pp 1838–1844

Aditya Maheshwari, P. S. S. Rao, William S. Messer Jr.*

Peptide-based immunoadsorbents: Molecular grafting of IgG–Fc-binding epitopes of Protein A onto a de novo-designedhelix-loop-helix peptide

pp 1845–1849

Kumiko Kawabata, Hirokazu Nagai, Nao Konishi, Daisuke Fujiwara, Ryo Sasaki, Takafumi Ichikawa, Ikuo Fujii*

Immunoadsorption therapy

1792 Contents / Bioorg. Med. Chem. 22 (2014) 1791–1796

Design, synthesis and biological evaluation of 7-nitro-1H-indole-2-carboxylic acid derivatives as allosteric inhibitors offructose-1,6-bisphosphatase

pp 1850–1862

Jianbo Bie, Shuainan Liu, Jie Zhou, Bailing Xu*, Zhufang Shen*

NH

O

OHNO2

R3R4

R5

A series of novel indole derivatives was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). Extensive structure–activity relationships were conducted and led to apotent FBPase inhibitor 3.9 with an IC50 of 0.99 lM. The binding mode of this series indoles was predicted using CDOCKER algorithm.

Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographicoverlays

pp 1863–1872

Wenmin Chen, Peng Zhan, Diwakar Rai, Erik De Clercq, Christophe Pannecouque, Jan Balzarini, Zhongxia Zhou, Huiqing Liu,Xinyong Liu*

N

NO NH

CN CN

BrNH2

TMC125

NHIO

O

SO

R221239

MolecularHybridization

NH

O NH

OX

R1R2

13

Hybrid 2-Pyridone NNRTIslead compounds

H, I, Br, Cl

Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydraseisoforms hCA IX and hCA XII

pp 1873–1882

SitaRam*, Gulsah Celik, Poonam Khloya, Daniela Vullo,Claudiu T. Supuran*, Pawan K. Sharma*

Novel heterocyclic compounds containing benzenesulfonamide moiety bearing 1,2,4-triazole scaffold showed excellent carbonic anhydrase hCA IX and hCA XII inhibitoryefficiency and also promising selectivity over hCA I and hCA II.

Study of anti-fibrillogenic activity of iron(II) clathrochelates pp 1883–1888

Vladyslava B. Kovalska*, Mykhaylo Yu. Losytskyy, Oleg A. Varzatskii, Vsevolod V. Cherepanov, Yan Z. Voloshin,Andriy A. Mokhir, Sergiy M. Yarmoluk, Sergiy V. Volkov

Contents / Bioorg. Med. Chem. 22 (2014) 1791–1796 1793

Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria pp 1889–1898

Li-Shian Shi, Sheng-Chu Kuo, Han-Dong Sun, Susan L. Morris-Natschke, Kuo-Hsiung Lee, Tian-Shung Wu*

O

OH

R1

R2R4

O

R3

H

H

O

OH

OHO

O

H

H

OH

7CH2OH

HO

OH

OHHO

H

H

8

O

OHOH

OH

CH3

Compd R1 R2 R3 R41 COOH OH H α-O-α-L-rhamnose2 OH OH H β-O-α-L-rhamnose3 OH OH H β-O-β-D-allomethylose4 OH OH OH β-O-α-L-rhamnose5 OH OH OH β-O-β-D-antiarose6 H H H β-O-α-L-rhamnose

Characterization of lovastatin–docosahexaenoate anticancer properties against breast cancer cells pp 1899–1908

Rafat A. Siddiqui*, Kevin A. Harvey, Zhidong Xu, Selvamuthu K. Natarajan, V. Jo Davisson

H3C

O

O

CH3

H3C H H

OH

CH3

O OH

+HO

O

O

O

H3C

O

O

CH3

H3C H H

OH

CH3

O

LOV DHA LOV-DHA

Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazolinederivatives as protein kinase inhibitors

pp 1909–1915

Digambar Kumar Waiker, Chandrabose Karthikeyan,Vasanthanathan Poongavanam, Jacob Kongsted, Olivier Lozach,Laurent Meijer, Piyush Trivedi*

The present work explores the utility of 4-anilino quinazoline, a privilegedscaffold as inhibitors of protein kinases implicated in neurodegenerativediseases.

Alkynyl–coumarinyl ethers as MAO-B inhibitors pp 1916–1928

Matthias D. Mertens, Sonja Hinz, Christa E. Müller*, Michael Gütschow*

O OO

OMeMAO-A IC50 > 10,000 nM

MAO-B IC50 = 2.96 nM

log D7.4 = 4.3

1794 Contents / Bioorg. Med. Chem. 22 (2014) 1791–1796

Synthesis, receptor affinity and effect on pentylenetetrazole-induced seizure threshold of novel benzodiazepineanalogues: 3-Substituted 5-(2-phenoxybenzyl)-4H-1,2,4-triazoles and 2-amino-5-(phenoxybenzyl)-1,3,4-oxadiazoles

pp 1929–1937

Siavash Mashayekh, Narges Rahmanipour, Behnaz Mahmoodi, Fatemeh Ahmadi, Dina Motaharian, Soraya Shahhosseini,Hamed Shafaroodi, Hamid R. Banafshe, Abbas Shafiee, Latifeh Navidpour*

OO

NN

NH2

XY

O

COOH

YX

O

CH2COOH

YX

OHN

NHN

YX

S OHN

NN

YX

SR

OHN

NN

YX

OCH2CH3

X = H, F, ClY = H, Cl

Development of novel tetrahydrothieno[2,3-c]pyridine-3-carboxamide based Mycobacterium tuberculosis pantothenatesynthetase inhibitors: Molecular hybridization from known antimycobacterial leads

pp 1938–1947

Ganesh Samala, Parthiban Brindha Devi, Radhika Nallangi, Jonnalagadda Padma Sridevi, Shalini Saxena,Perumal Yogeeswari, Dharmarajan Sriram*

Development of novel silicon-containing inverse agonists of retinoic acid receptor-related orphan receptors pp 1948–1959

Hirozumi Toyama*, Masaharu Nakamura, Masahiko Nakamura, Yotaro Matsumoto, Madoka Nakagomi, Yuichi Hashimoto

NH

CO2HO

Am580

Screening ofROR inverse agonist

O

Compound 3

Structural development

Si

Si

NH

O

Compound 22ROR inverse agonist

IC50=1.3 μM (RORα), >10 μM (RORβ), 4.5 μM (RORγ)

O

OH

all-trans -retinoic acid (ATRA)RAR agonist and

RORβ inverse agonist

Novel compounds lowering the cellular isoform of the human prion protein in cultured human cells pp 1960–1972

B. Michael Silber, Joel R. Gever, Satish Rao, Zhe Li, Adam R. Renslo, Kartika Widjaja, Casper Wong, Kurt Giles,Yevgeniy Freyman, Manuel Elepano, John J. Irwin, Matthew P. Jacobson, Stanley B. Prusiner*

Contents / Bioorg. Med. Chem. 22 (2014) 1791–1796 1795

*Corresponding authorSupplementary data available via ScienceDirect

COVER

Botulinum neuortoxins are the most lethal toxins known to man and are considered by the Centers for Disease Control and Prevention (CDC) tobe a ‘‘Category A’’ agent placing them as one of the six highest priority bioterrorist agents. There are no approved pharmacological treatmentsfor botulinum neurointoxication. The work detailed combines studies using synthesis, crystallography, modeling, kinetic and cellular researchto advance pharmacological intervention against this neurotoxin. [Šilhár, P.; Silvaggi, N.R.; Pellett, S.; Capková, K.; Johnson, E.A; Allen, K.N;Janda, K.D. Bioorg. Med. Chem. 2013, 21, 1344–1348].

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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 Scopus�. Full text available on ScienceDirect�

ISSN 0968-0896

1796 Contents / Bioorg. Med. Chem. 22 (2014) 1791–1796