Novel isoniazid derivative as promising antituberculosis agent.
Galyna P VolynetsMichael A TukaloVolodymyr G BdzholaNataliia M DerkachMykola I GumeniukSergiy S TarnavskiySergiy M YarmolukPublished in: Future microbiology (2020)
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.
Keyphrases
- mycobacterium tuberculosis
- drug resistant
- induced apoptosis
- pulmonary tuberculosis
- drug discovery
- multidrug resistant
- cell cycle arrest
- acinetobacter baumannii
- escherichia coli
- endoplasmic reticulum stress
- stem cells
- oxidative stress
- high throughput
- binding protein
- cystic fibrosis
- amino acid
- hepatitis c virus
- cell proliferation
- transcription factor
- small molecule
- single molecule
- protein protein
- atomic force microscopy
- hiv infected