Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies

Ahmed A. Al-Karmalawy; Dalia S. El-Gamil; Rabeh El-Shesheny; Marwa Sharaky; Radwan Alnajjar; Omnia Kutkat; Yassmin Moatasim; Mohamed Elagawany; Sara T. Al-Rashood; Faizah A. Binjubair; Wagdy M. Eldehna; Ayman M. Noreddin; Mohamed Y. Zakaria

doi:10.1080/14756366.2023.2202357

Journal of Enzyme Inhibition and Medicinal Chemistry (Dec 2023)

Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies

Ahmed A. Al-Karmalawy,
Dalia S. El-Gamil,
Rabeh El-Shesheny,
Marwa Sharaky,
Radwan Alnajjar,
Omnia Kutkat,
Yassmin Moatasim,
Mohamed Elagawany,
Sara T. Al-Rashood,
Faizah A. Binjubair,
Wagdy M. Eldehna,
Ayman M. Noreddin,
Mohamed Y. Zakaria

Affiliations

Ahmed A. Al-Karmalawy: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
Dalia S. El-Gamil: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
Rabeh El-Shesheny: Water Pollution Research Department, The Center of Scientific Excellence for Influenza Viruses, Environmental Research Institute, National Research Centre, Giza, Egypt
Marwa Sharaky: Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt
Radwan Alnajjar: Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi, Libya
Omnia Kutkat: Water Pollution Research Department, The Center of Scientific Excellence for Influenza Viruses, Environmental Research Institute, National Research Centre, Giza, Egypt
Yassmin Moatasim: Water Pollution Research Department, The Center of Scientific Excellence for Influenza Viruses, Environmental Research Institute, National Research Centre, Giza, Egypt
Mohamed Elagawany: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
Sara T. Al-Rashood: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Faizah A. Binjubair: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Wagdy M. Eldehna: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
Ayman M. Noreddin: Department of Internal Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA
Mohamed Y. Zakaria: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Said, Egypt

DOI: https://doi.org/10.1080/14756366.2023.2202357
Journal volume & issue: Vol. 38, no. 1

Abstract

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In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a–3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a–g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 μg/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure–activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.

Published in Journal of Enzyme Inhibition and Medicinal Chemistry

ISSN: 1475-6366 (Print); 1475-6374 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.tandfonline.com/journals/ienz

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