Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR(WT) and EGFR(T790M) inhibitors

Tarfah Al-Warhi; Ahmed A. Al-Karmalawy; Ayman Abo Elmaaty; Maha A. Alshubramy; Marwa Abdel-Motaal; Taghreed A. Majrashi; Medhat Asem; Ahmed Nabil; Wagdy M. Eldehna; Marwa Sharaky

doi:10.1080/14756366.2022.2135512

Back

Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR(WT) and EGFR(T790M) inhibitors

Journal article

Open access

Peer reviewed

Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR(WT) and EGFR(T790M) inhibitors

Tarfah Al-Warhi, Ahmed A. Al-Karmalawy, Ayman Abo Elmaaty, Maha A. Alshubramy, Marwa Abdel-Motaal, Taghreed A. Majrashi, Medhat Asem, Ahmed Nabil, Wagdy M. Eldehna and Marwa Sharaky

Journal of enzyme inhibition and medicinal chemistry, Vol.38(1), pp.176-191

01/01/2023

DOI: https://doi.org/10.1080/14756366.2022.2135512

PMID: 36317648

Abstract

Biochemistry & Molecular Biology

Chemistry, Medicinal

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.

Files and links (1)

url

https://doi.org/10.1080/14756366.2022.2135512View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR(WT) and EGFR(T790M) inhibitors
Creators - without role: Tarfah Al-Warhi - Princess Nourah bint Abdulrahman University
Ahmed A. Al-Karmalawy - Ahram Canadian University
Ayman Abo Elmaaty - Port Said University
Maha A. Alshubramy - Qassim University
Marwa Abdel-Motaal - Qassim University
Taghreed A. Majrashi - King Khalid University
Medhat Asem - College of Engineering and Information Technology, Onaizah Colleges, Al-Qassim, Saudi Arabia
Ahmed Nabil - National Institute for Materials Science
Wagdy M. Eldehna - Kafrelsheikh University
Marwa Sharaky - Cairo University
Publication Details: Journal of enzyme inhibition and medicinal chemistry, Vol.38(1), pp.176-191
Publisher: Taylor & Francis
Number of pages: 16
Grant note: PNURSP2022R25 / Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; Princess Nourah bint Abdulrahman University RGP.1/346/43 / Deanship of Scientific Research at King Khalid University
Identifiers: 9923800908331
Academic Unit: King Khalid University; Princess Nourah bint Abdulrahman University; Qassim University
Language: English
Resource Type: Journal article