Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

• Main Authors: Lagu, Surendra Babu, Yejella, Rajendra Prasad, Nissankararao, Srinath, Bhandare, Richie R., Golla, Venu Sampath, Lokesh, Bontha Venkata Subrahmanya, Rahman, M. Mukhlesur, Shaik, Afzal Basha
• Format: Article
• Published: Public Library of Science 2022
• Subjects: RM Therapeutics. Pharmacology
• Online Access: http://eprints.um.edu.my/41493/

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC similar to 8 mu M) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC-16-18 mu M). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro M IC value (similar to 8 mu M). These findings suggest that 2-aminopyridine-3-carbonitrile and 2amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs.