Isoflavonoid and Furanochromone Natural Products as Potential DNA Gyrase Inhibitors: Computational, Spectral, and Antimycobacterial Studies.

Autor: Jagatap VR; Division of Computer-Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur District, Dhule 425405, Maharashtra, India., Ahmad I; Division of Computer-Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur District, Dhule 425405, Maharashtra, India., Sriram D; Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R. R. District, Hyderabad 500078, India., Kumari J; Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R. R. District, Hyderabad 500078, India., Adu DK; Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban 4000, South Africa., Ike BW; Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban 4000, South Africa., Ghai M; Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa., Ansari SA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Ansari IA; Department of Drug Science and Technology, University of Turin, Turin 10124, Italy., Wetchoua POM; Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban 4000, South Africa., Karpoormath R; Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban 4000, South Africa., Patel H; Division of Computer-Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur District, Dhule 425405, Maharashtra, India.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2023 Apr 28; Vol. 8 (18), pp. 16228-16240. Date of Electronic Publication: 2023 Apr 28 (Print Publication: 2023).
DOI: 10.1021/acsomega.3c00684
Abstrakt: In pursuit of new antitubercular agents, we here report the antimycobacterial (H 37 Rv) and DNA gyrase inhibitory potential of daidzein and khellin natural products (NPs). We procured a total of 16 NPs based on their pharmacophoric similarities with known antimycobacterial compounds. The H 37 Rv strain of M. tuberculosis was found to be susceptible to only two out of the 16 NPs procured; specifically, daidzein and khellin each exhibited an MIC of 25 μg/mL. Moreover, daidzein and khellin inhibited the DNA gyrase enzyme with IC 50 values of 0.042 and 0.822 μg/mL, respectively, compared to ciprofloxacin with an IC 50 value of 0.018 μg/mL. Daidzein and khellin were found to have lower toxicity toward the vero cell line, with IC 50 values of 160.81 and 300.23 μg/mL, respectively. Further, molecular docking study and MD simulation of daidzein indicated that it remained stable inside the cavity of DNA GyrB domain for 100 ns.
Competing Interests: The authors declare no competing financial interest.
(© 2023 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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