Novel isoniazid derivative as promising antituberculosis agent.

A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of . We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound , which potentially exhibits pharmacologic effects, is 57.9%. Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.