Novel isoniazid derivative as promising antituberculosis agent.

Abstract:

: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; IC50 >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.

journal_name

Future Microbiol

journal_title

Future microbiology

authors

Volynets GP,Tukalo MA,Bdzhola VG,Derkach NM,Gumeniuk MI,Tarnavskiy SS,Yarmoluk SM

doi

10.2217/fmb-2019-0085

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

869-879

eissn

1746-0913

issn

1746-0921

journal_volume

15

pub_type

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