SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 3-HYDRAZONO-1H-2-INDOLINONES WITH ANTITUBERCULOSIS ACTIVITY

A series of 3-[S-(4-substituted substituted-isothiosemicarbazono]-1H-2 -indolinones 2a-h and -4-thiazolin-2-ylidene)hydrazono]-1H-2-indolinon es 3a-f were synthesized. These new hydrazonoindolinone derivatives an d tuted-thiosemicarbazono)-1H/1-acetyl-2-indolinones 1a-g 3-[(2-substi tuted-4-thiazolidinon-2-ylid drazono]-1H-2-indolinones 4a-o, -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 again st Mycobacterium tuberculosis H37Rv. These compounds exhibited varying degrees of inhibition in the in vitro primary screening that was cond ucted 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 demo nstrating activity in the primary screen were re-tested at lower conce ntrations against M. tuberculosis H37Rv to determine the actual minimu m inhibitory concentration (MIC) in CABTEC 460. The structure-activity relationships of the derivatives were investigated.