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

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.