Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from Zanthoxylum rhetsa (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro)

Fatema Tuz Zohora; A T M Zafrul Azam; Sinthyia Ahmed; Khondaker Miraz Rahman; Mohammad A Halim; Md Rafi Anwar; Md Hossain Sohrab; Fatema Tabassum; Choudhury Mahmood Hasan; Monira Ahsan

doi:10.3390/molecules27238191

Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from Zanthoxylum rhetsa (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro)

Molecules. 2022 Nov 24;27(23):8191. doi: 10.3390/molecules27238191.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
² Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Dhaka 1205, Bangladesh.
³ Division of Computer Aided Drug Design, The Red-Green Research Centre, BICCB, Tejgaon, Dhaka 1219, Bangladesh.
⁴ School of Cancer and Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
⁵ Department of Chemistry and Biochemistry, Kennesaw State University, Kennesaw, GA 30144, USA.
⁶ College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
⁷ Bangladesh Council of Scientific and Industrial Research (BCSIR), Dr. Qudrat-E-Khuda Road, Dhaka 1205, Bangladesh.
⁸ Department of Pharmacy, Stamford University Bangladesh, 51 Siddheswari Rd, Dhaka 1217, Bangladesh.

Abstract

A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of -8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro.

Keywords: 2,11-didemethoxy-vepridimerine A; 2-quinolone; SARS-CoV-2 (Mpro); Zanthoxylum rhetsa; benzophenanthridine alkaloids.

MeSH terms

Alkaloids* / pharmacology
Antineoplastic Agents*
COVID-19*
Molecular Docking Simulation
Molecular Dynamics Simulation
Polymers
Protease Inhibitors
Quinolones*
SARS-CoV-2
Zanthoxylum*

Substances

Quinolones
Alkaloids
Polymers
Antineoplastic Agents
Protease Inhibitors

Grants and funding

The research was funded by University of Dhaka, Dhaka 1000, Bangladesh.