Issue 56, 2020

Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins

Abstract

The 2019 coronavirus (COVID-19) pandemic is spreading worldwide, with a dramatic increase in death without any effective therapeutic treatment available up to now. We previously reported quinazoline-trihydroxyphenyl Schiff base conjugates as phosphodiesterase 4B (PDE 4B) inhibitors (an enzyme that plays an essential role in the early stages of COVID-19 pneumonia). Additionally, the structural similarity between these conjugates and identified anti-severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 flavonoids inspired us to in silico study their possible binding interactions with essential SARS-CoV-2 proteins. Thus, this study provides an insight into the potential bindings between quinazoline-Schiff base conjugates and SARS-CoV-2 proteins, including spike glycoprotein (SGp), main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), to offer an opportunity to find an effective therapy. Besides this, based on the role that COVID-19 plays in iron dysmetabolism, the conjugate trihydroxyphenyl moiety should be reconsidered as an iron chelator. Moreover, molecular dynamics simulations of quinazoline derivative Ic bound to the mentioned targets were carried out. Finally, ADMET calculations were performed for the studied compounds to predict their pharmacokinetic profiles.

Graphical abstract: Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins

Article information

Article type
Paper
Submitted
23 Jul 2020
Accepted
02 Sep 2020
First published
15 Sep 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 34033-34045

Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins

M. A. Mansour, A. M. AboulMagd and H. M. Abdel-Rahman, RSC Adv., 2020, 10, 34033 DOI: 10.1039/D0RA06424F

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements