Original Article

Role of Cephalosporins in Targeting SLC7A11/xCT through In-silico-assisted Virtual screening: Underline Molecular Mechanism and Possibility of Innovative Treatment in Preventing Cardiotoxicity.

Saif sultan Alsahli, Awid mshain Almutiry, Obaid faris Aldossari, Nada abdullah Alotaibi, Norah musallam Aldosari, Albandari saad Almutairi, Haya mohammed Alqahtani, Fahad sari Alanazi, Abdulrahman ibraihm Alzmael, Mohammed abdullah Alsugairan, Abrar Alasmari.

Author Information

Ministry of National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.

Nursing Department, Primary health care, Ministry of National Guard-Health Affairs, Dirab, Riyadh, Kingdom of Saudi Arabia.

Aviation medicine unit, Ministry of National Guard-Health Affairs, Riyadh, Kingdom of Saudi Arabia.

Medical record Department, Primary health care, Ministry of National Guard-Health Affairs, Dirab, Riyadh, Kingdom of Saudi Arabia.

Address for correspondence: Abrar Alasmari. King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia.

Email: Abrar.alasmari@outlook.com

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 4.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cardiotoxicity is cardiomyopathy, which is characterized by a global or more severe decrease in left ventricular ejection fraction (LVEF), a decline in ejection fraction (EF) of less than 5% to a final ejection fraction of less than 55% with congestive heart failure symptoms, or an asymptomatic decline of LVEF of less than 10% to a final ejection fraction of less than 55%. This study explores a novel therapeutic approach for cardiotoxicity by targeting cystine/glutamate antiporter (xCT), whose responsibility is to exchange cystine/glutamate with cystine entering cells in conjunction with the release of glutamate in a ratio 1:1. The preservation of glutathione (GSH) levels inside cells by enhancing intracellular cysteine which is well known precursor for GSH synthesis is necessary for cells defending against oxidative stress. A total number of sixteen Ligands were chosen from different cephalosporins generations for molecular docking against xCT, 2 com-pounds ceftriaxone and ceftobiprole exhibited superior binding affinities compared to the other cephalosporins. These findings indicate that these compounds could modulate xCT activity. This study provides essential insights into protein-ligand interactions and establishes a foundation for further research to advance these compounds towards clinical application.

Keywords: Molecular docking; Cysteine/glutamate antiporter; Cephalosporins; Cardiotoxicity.

American Journal of Molecular Signaling