Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV-TB co-infection

被引：120

作者：

Banerjee, Debjani ^{[1
]}

Yogeeswari, Perumal ^{[1
]}

Bhat, Pritesh ^{[1
]}

Thomas, Anisha ^{[1
]}

Srividya, Madala ^{[1
]}

Sriram, Dharmarajan ^{[1
]}

机构：

[1] Birla Inst Technol & Sci Pilani, Pharm Grp, Med Chem & Antimycobacterial Res Lab, Hyderabad 500078, Andhra Pradesh, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 01期

关键词：

Isatin; Mannich base; HIV-TB co-infection; Isocitrate lyase; REVERSE-TRANSCRIPTASE INHIBITORS; SPECTRUM CHEMOTHERAPEUTIC PROPERTIES; VIRAL MESSENGER-RNA; MYCOBACTERIUM-TUBERCULOSIS; ISOCITRATE LYASE; BETA-THIOSEMICARBAZONE; INVITRO TRANSLATION; DRUG MOLECULES; DESIGN; VIRUS;

D O I：

10.1016/j.ejmech.2010.10.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 5-substituted-1-(arylmethyl/alkylmethyl)-1H-indole-2,3-dione-3-(N-hydroxy/methoxy thiosemicarbazone) analogues were synthesized and evaluated for their anti-HIV activity and anti-tubercular activity in both log phase and starved cultures. The compound 2-(1-([4-(4-chlorophenyl)tetrahydropyrazin-1 (2H)-yl]methyl)-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-yliden)-N-(methyloxy)hydrazine-1-carbothioamide (B21) displayed promising activity against the replication of HIV-1 cells (EC50 1.69 mu M). In anti-mycobacterial screening B21 proved effective in inhibiting the growth of both log phase (MIC 330 mu M) and starved (MIC 12.11 mu M) MTB cultures. Isocitrate lyase enzyme having momentous implication in persistent TB was shown to be inhibited by 1-cyclopropyl-6-fluoro-7-[4-{[5-methyl-3-((Z)-2-{[(methyloxy)amino]carbothioyl} hydrazono)-2-oxo-1H-indol-1(2H)-yl]methyl}tetrahydropyrazin-1(2H)-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (B30) with 63.44% inhibition at 10 mM. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：106 / 121

页数：16

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