Synthesis and investigation of anti-COVID19 ability of ferrocene Schiff base derivatives by quantum chemical and molecular docking

Ghulam Abbas; Ahmad Irfan; Ishtiaq Ahmed; Firas Khalil Al-Zeidaneen; S Muthu; Olaf Fuhr; Renjith Thomas

doi:10.1016/j.molstruc.2021.132242

Synthesis and investigation of anti-COVID19 ability of ferrocene Schiff base derivatives by quantum chemical and molecular docking

J Mol Struct. 2022 Apr 5:1253:132242. doi: 10.1016/j.molstruc.2021.132242. Epub 2021 Dec 24.

Authors

Ghulam Abbas¹, Ahmad Irfan^{2

3}, Ishtiaq Ahmed⁴, Firas Khalil Al-Zeidaneen⁵, S Muthu⁶, Olaf Fuhr⁷, Renjith Thomas⁸

Affiliations

¹ Institute of Inorganic Chemistry, Karlsruhe Institute of Technology, Engesserstrasse 15, 76131 Karlsruhe, Germany.
² Research Center for Advanced Materials Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
³ Department of Chemistry, College of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
⁴ Department of Chemical Engineering and Biotechnology (CEB) Philippa Fawcett Drive, University of Cambridge, Cambridge CB3 0AS, UK.
⁵ Department of Chemistry and Chemical Technology, Taflia Technical University, Taflia, Jordon.
⁶ Department of Physics, Aringnar Anna Govt. Arts College, Cheyyar, 604407, Tamilnadu, India.
⁷ Institute of Nanotechnology, Karlsruhe Institute of Technology, Hermann von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
⁸ Department of Chemistry, St Berchmans College (Autonomous), Changanassery, Kerala, India.

Abstract

The recent outbreak of coronavirus disease (COVID-19) has rampaged the world with more than 236 million confirmed cases and over 4.8 million deaths across the world reported by the world health organization (WHO) till Oct 5, 2021. Due to the advent of different variants of coronavirus, there is an urgent need to identify effective drugs and vaccines to combat rapidly spreading virus varieties across the globe. Ferrocene derivatives have attained immense interest as anticancer, antifungal, antibacterial, and antiparasitic drug candidates. However, the ability of ferrocene as anti-COVID-19 is not yet explored. Therefore, in the present work, we have synthesized four new ferrocene Schiff bases (L1-L4) to understand the active sites and biological activity of ferrocene derivatives by employing various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential, and molecular electrostatic potential (MEP). A theoretical insight on synthesized ferrocene Schiff bases was accomplished by molecular docking, frontier molecular orbitals energies, active sites, and molecular descriptors which were further compared with drugs being currently used against COVID-19, i.e., dexamethasone, hydroxychloroquine, favipiravir (FPV), and remdesivir (RDV). Moreover, through the molecular docking approach, we recorded the inhibitions of ferrocene derivatives on core protease (6LU7) protein of SARS-CoV-2 and the effect of substituents on the anti-COVID activity of these synthesized compounds. The computational outcome indicated that L1 has a powerful 6LU7 inhibition of SARS-CoV-2 compared to the currently used drugs. These results could be helpful to design new ferrocene compounds and explore their potential application in the prevention and treatment of SARS-CoV-2.

Keywords: Anti-COVID19; Ferrocene derivatives; Molecular descriptors; Molecular docking.