Journal
MOLECULES
Volume 20, Issue 5, Pages 8800-8815Publisher
MDPI
DOI: 10.3390/molecules20058800
Keywords
synthesis; nicotinic acid; hydrazides; antimycobacterial; ADME
Funding
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
- Deanship of Scientific Research at King Saud University [RGP-VPP-321]
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Three series of 6-aryl-2-methylnicotinohydrazides 4a-i, N-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 mu g/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
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