Synthesis and structure-activity relationships of 3-hydrazono-1H-2-indolinones with antituberculosis activity

Abstract

A series of 3-[S-(4-substituted phenacyl)-4-substituted-isothiosemicarbazono]-1H-2-indolinones 2a-h and 3-[(3,4-disubstituted-4-thiazolin-2-ylidene)hydrazono]-1H-2-indolinones 3a-f were synthesized. These new hydrazonoindolinone derivatives and 3-(4-substituted-thiosemicarbazono)-1H/1-acetyl-2-indolinones 1a-g 3-[(2-substituted-4-thiazolidinon-2-ylid drazono]-1H-2-indolinones 4a-o, 3-[(2-substituted-4-carboxy/carbetoxy-5-methyl-4-thiazolin-2-ylidene) hydrazono]-1H-2-indolinones 5a-e and 3-substituted-hydrazono-1H-2-indolinones 6a-o which had been previously reported were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv. These compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at 12 mu g/ml against M. tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. 2a, 2c, 2f-h, 3c and 3f demonstrating activity in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv to determine the actual minimum inhibitory concentration (MIC) in CABTEC 460. The structure-activity relationships of the derivatives were investigated.