Abstract

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a3g) 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 (F3ag) 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.

Details

Title
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
Author
Al-Karmalawy, Ahmed A 1   VIAFID ORCID Logo  ; El-Gamil, Dalia S 1 ; El-Shesheny, Rabeh 2 ; Sharaky, Marwa 3 ; Alnajjar, Radwan 4 ; Kutkat, Omnia 2 ; Moatasim, Yassmin 2 ; Elagawany, Mohamed 5 ; Al-Rashood, Sara T 6 ; Binjubair, Faizah A 6 ; Eldehna, Wagdy M 7   VIAFID ORCID Logo  ; Noreddin, Ayman M 8 ; Zakaria, Mohamed Y 9 

 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt 
 Water Pollution Research Department, The Center of Scientific Excellence for Influenza Viruses, Environmental Research Institute, National Research Centre, Giza, Egypt 
 Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt 
 Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi, Libya; Faculty of Pharmacy, Libyan International Medical University, Benghazi, Libya; Department of Chemistry, University of Cape Town, Rondebosch, South Africa 
 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt 
 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia 
 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt; School of Biotechnology, Badr University in Cairo, Badr City, Egypt 
 Department of Internal Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA; Department of Clinical Pharmacy, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt 
 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Said, Egypt 
Publication year
2023
Publication date
Dec 2023
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2917546796
Copyright
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.