Exploring 4-substituted-2-thiazolylhydrazones from 2-, 3-, and 4-acetylpyridine as selective and reversible hMAO-B inhibitors

被引：27

作者：

Chimenti, Paola ^{[1
]}

Petzer, Anel ^{[2
,3
]}

Carradori, Simone ^{[1
]}

D'Ascenzio, Melissa ^{[1
]}

Silvestri, Romano ^{[1
]}

Alcaro, Stefano ^{[4
]}

Ortuso, Francesco ^{[4
]}

Petzer, Jacobus P. ^{[2
,3
]}

Secci, Daniela ^{[1
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, I-00185 Rome, Italy

[2] North West Univ, Sch Pharm, ZA-2520 Potchefstroom, South Africa

[3] North West Univ, Sch Pharm, Unit Drug Res & Dev, ZA-2520 Potchefstroom, South Africa

[4] Magna Graecia Univ Catanzaro, Dipartimento Sci Salute, I-88100 Catanzaro, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 66卷

关键词：

Monoamine oxidase; Acetylpyridine; Reversibility; Molecular modelling; Thiazole; MONOAMINE-OXIDASE-B; BIOLOGICAL EVALUATION; ACCURATE DOCKING; MAO; GLIDE; DERIVATIVES; PROTEINS; SCAFFOLD;

D O I：

10.1016/j.ejmech.2013.05.032

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A series of 4-substituted-2-thiazolylhydrazone derivatives have been synthesized and tested in vitro for their human monoamine oxidase (hMAO) A and B inhibitory activity. Our findings confirmed that the substitution at C4 of the thiazole ring was important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Moreover, these derivatives were endowed with a reversible mechanism of enzyme inhibition. Molecular modelling studies were performed to rationalize the recognition of all inhibitors with respect to hMAO-A and -B isoforms. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：221 / 227

页数：7

共 44 条

[1]

[Anonymous], 2010, MACROMODEL VERS 9 8

[2]

[Anonymous], 2010, DESM MOL DYN SYST VE

[3]

[Anonymous], 2010, GLID VERS 5 6

[4]

[Anonymous], 2010, MAESTR VERS 9 1

[5]

The Protein Data Bank [J].

Berman, HM ;

Westbrook, J ;

Feng, Z ;

Gilliland, G ;

Bhat, TN ;

Weissig, H ;

Shindyalov, IN ;

Bourne, PE .

NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242

[6]

Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs [J].

Binda, Claudia ;

Wang, Jin ;

Pisani, Leonardo ;

Caccia, Carla ;

Carotti, Angelo ;

Salvati, Patricia ;

Edmondson, Dale E. ;

Mattevi, Andrea .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (23) :5848-5852

[7]

Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Antidiabetes Drugs [J].

Binda, Claudia ;

Aldeco, Milagros ;

Geldenhuys, Werner J. ;

Tortorici, Marcell ;

Mattevi, Andrea ;

Edmondson, Dale E. .

ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (01) :39-42

[8]

Blandini F, 2005, CNS DRUG REV, V11, P183

[9]

Recent development of monoamine oxidase inhibitors [J].

Bolasco, A ;

Fioravanti, R ;

Carradori, S .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (12) :1763-1782

[10]

Focusing on new monoamine oxidase inhibitors [J].

Bolasco, Adriana ;

Carradori, Simone ;

Fioravanti, Rossella .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2010, 20 (07) :909-939

← 1 2 3 4 5 →