Ferrocenyl Hydroxy Methyl Coupled Caffeine Synthesis, Density Functional Theory, ADME Prediction and Docking Analysis of It's Binding Interactions to Coronavirus Main Protease-Reference-Cited by-同舟云学术

Ferrocenyl Hydroxy Methyl Coupled Caffeine Synthesis, Density Functional Theory, ADME Prediction and Docking Analysis of It's Binding Interactions to Coronavirus Main Protease

Published:2023-04-30 Issue:2 Volume:39 Page:222-230
ISSN:2231-5039
Container-title:Oriental Journal Of Chemistry
language:en
Short-container-title:Orient. J. Chem

Author:

Almahmoud Sondos Abdullah J¹^ORCID,Cariello Michele²^ORCID,Elzupir Amin Osman¹^ORCID

Affiliation:

1. 1Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.

2. 2West CHEM, School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK.

Abstract

The COVID-19 pandemic has made the World aware of how crucial the development of cost-effective and scalable antiviral drugs is. Here we report the synthesis of caffeine-based 8-[(ferrocenyl)(hydroxy)methyl]-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (FHC), and its use as an inhibitor of protease (Mpro), an essential enzyme for SARS-CoV-2 viral replication. FHC was modelled through density functional theory to get an insight of its properties, and fully characterized through conventional techniques. Its activity against Mpro was investigated using a molecular docking approach, showing excellent binding affinity to the catalytic dyad of His41 and Cys145 and the active sites of Mpro with energies score ranging from −6.7 to −7.0 kcal/mol. The affinity of conformers to bind to the active pocket was 44%. Based on a detailed investigation, it appears that FHC has a safe ADME profile, and that it could be a potential inhibitor for Mpro of SARS-CoV-2.

Publisher

Oriental Scientific Publishing Company

Subject

Drug Discovery,Environmental Chemistry,Biochemistry,General Chemistry

Reference53 articles.

1. Faudone, G.; Arifi, S.; Merk, D., The Medicinal Chemistry of Caffeine. Journal of medicinal chemistry 2021, 64 (11), 7156-7178.

2. Davies-Strickleton, H.; Cook, J.; Hannam, S.; Bennett, R.; Gibbs, A.; Edwards, D.; Ridden, C.; Ridden, J.; Cook, D., Assessment of the nail penetration of antifungal agents, with different physico-chemical properties. PLOS ONE 2020, 15 (2), e0229414.

3. Wilkinson, S. C.; Maas, W. J. M.; Nielsen, J. B.; Greaves, L. C.; van de Sandt, J. J. M.; Williams, F. M., Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. International Archives of Occupational and Environmental Health 2006, 79 (5), 405-413.

4. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 1997, 23 (1), 3-25.

5. Institute of Medicine Committee on Military Nutrition, R., In Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations, National Academies Press (US). Copyright 2001 by the National Academy of Sciences. All rights reserved.: Washington (DC), 2001.