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

Abstract

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 (EC(50) 1.69 μM). In anti-mycobacterial screening B21 proved effective in inhibiting the growth of both log phase (MIC 3.30 μM) and starved (MIC 12.11 μM) 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.

• Authors: Debjani Banerjee, Perumal Yogeeswari, Pritesh Bhat, Anisha Thomas, Madala Srividya, Dharmarajan Sriram
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 1 Pg. 106-21 (Jan 2011) ISSN: 1768-3254 [Electronic] France
• PMID: 21093117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Anti-HIV Agents
• Thiosemicarbazones
• reverse transcriptase, Human immunodeficiency virus 1
• HIV Reverse Transcriptase
• Isocitrate Lyase

Topics

• Anti-Bacterial Agents (chemistry, metabolism, pharmacology, therapeutic use)
• Anti-HIV Agents (chemistry, metabolism, pharmacology, therapeutic use)
• Cell Line
• HIV (drug effects, enzymology, physiology)
• HIV Infections (drug therapy)
• HIV Reverse Transcriptase (antagonists & inhibitors, chemistry, metabolism)
• Isocitrate Lyase (antagonists & inhibitors, chemistry, metabolism)
• Models, Molecular
• Molecular Conformation
• Mycobacterium tuberculosis (drug effects, enzymology, physiology)
• Thiosemicarbazones (chemistry, metabolism, pharmacology, therapeutic use)
• Tuberculosis (drug therapy)