Open AccessNovel isoniazid derivative as promising antituberculosis agent
Author(s) -
Galyna P. Volynets,
M. A. Tukalo,
Volodymyr G. Bdzhola,
Н. М. Деркач,
Mykola Gumeniuk,
S. S. Tarnavskiy,
S. M. Yarmoluk
Publication year - 2020
Publication title -
future microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.797
H-Index - 82
eISSN - 1746-0921
pISSN - 1746-0913
DOI - 10.2217/fmb-2019-0085
Subject(s) - isoniazid , isonicotinic acid , mycobacterium tuberculosis , hydrazide , tuberculosis , chemistry , drug , minimum inhibitory concentration , antibiotics , pharmacology , antimicrobial , microbiology and biotechnology , biochemistry , medicine , biology , organic chemistry , pathology
Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis . Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide ( 1 ), 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 50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1 , which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.