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.

Autor: Lagu SB; Pharmaceutical Chemistry Division, Adikavi Nannaya University College of Pharmaceutical Sciences, Adikavi Nannaya University, Tadepalligudem, Andhra Pradesh, India., Yejella RP; Department of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India., Nissankararao S; Montvale, New Jersey, New Jersey, United States of America., Bhandare RR; Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Ajman University, Ajman, United Arab Emirates.; Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates., Golla VS; Department of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India., Subrahmanya Lokesh BV; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia., Rahman MM; Medicines Research Group, School of Health, Sports and Bioscience, University of East London, London, United Kingdom., Shaik AB; Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Jawaharlal Nehru Technological University, Vadlamudi, Andhra Pradesh, India.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Jun 16; Vol. 17 (6), pp. e0265068. Date of Electronic Publication: 2022 Jun 16 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0265068
Abstrakt: A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) 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 μM). 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 MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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