In vitro and in silico exploration of newly synthesized triazolyl- isonicotinohydrazides as potent antitubercular agents.

In the present study, we have reported the synthesis of novel isoniazid-triazole derivatives (4a-r), via the click chemistry approach. The synthesized isoniazid-triazole derivatives have potent in vitro antitubercular activity against the Mycobacterium tuberculosis (MTB) H37Rv strain. Among these compounds, 4b, 4f, 4g, 4j, 4k, 4m, 4o, 4p, and 4r were found to be the most active ones with a MIC value of 0.78 µg/mL. This activity is better than ciprofloxacin (MIC value = 1.56 µg/mL) and ethambutol (MIC value = 3.12 µg/mL). The compounds, 4a, 4c, 4d, 4e, 4h, 4i, 4l, and 4n have displayed activity equal to ciprofloxacin (MIC value = 1.56 µg/mL). The cytotoxicity of the active isoniazid-triazole derivatives was studied against RAW 264.7 cell line by MTT assay at 25 µg/mL concentration and no toxicity was observed. Moreover, in-vitro results were supported by in-silico studies with the known antitubercular target (PanK). The drug-likeness, density functional study, molecular docking, and molecular dynamics simulation studies of isoniazid-triazole derivatives validated the ability to form a stable complex with Pantothenate kinase (PanK), which will result in inhibiting the Pantothenate kinase (PanK). Therefore, the results obtained indicate that this class of compounds may offer candidates for future development, and positively provide drug alternatives for tuberculosis treatment.Communicated by Ramaswamy H. Sarma.

Design and synthesis of new indanol-1,2,3-triazole derivatives as potent antitubercular and antimicrobial agents.

In a search of new antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent antitubercular agent with MIC value 1.56 µM. The most active compounds of the series were further studied for their cytotoxicity against HEK 293 cells using MTT assay and found to be nontoxic. In addition, ten compounds were shown good antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study against Mycobacterial enoyl-ACP-reductase (InhA) was performed to gain an insight into the molecular mechanism of antitubercular action. The pharmacokinetic parameters of these compounds were studied and displayed acceptable drug-likeness score.