Synthesis of carbohydrazides and carboxamides as anti-tubercular agents

A novel series of furan/thiophene carbohydrazides and carboxamides were synthesized and evaluated for anti-TB and cytotoxic activities. All the synthesized compounds were characterized using H-1 and C-13 NMR and mass spectral techniques. Among the 23 compounds tested for anti-tubercular activity, seven compounds (3e, 3g, 3h, 9b, 9c, 9e and 9h) showed minimum inhibitory concentration value less than 1 mu g/mL against Mycobacterium tuberculosis H37Rv and they were found to be non-toxic. Molecular docking and dynamics simulation studies of these compounds with an enzyme enoyl ACP reductase revealed the probable mechanism of action, which is similar to isoniazid. Further, all these tested compounds exhibited good absorption, distribution, metabolism and excretion and drug-likeness in-silico and thus may be considered as potential leads for further drug development. (C) 2018 Elsevier Masson SAS. All rights reserved.