Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity

Faculty of Pharmacy

Assiut University

Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity

Research Authors
Fatma A. M. Mohamed, Hesham A.M. Gomaa, Hendawy OM, Asmaa T. Ali, Hatem S. Farghaly, Ahmed M. Gouda, Ahmed H. Abdelazeem, Mostafa H. Abdelrahman, Laurent Trembleau, Bahaa G. M. Youssif
Research Date
Research Department
Department of Pharmaceutical Organic Chemistry
Research Journal
Bioorganic Chemistry
Research Publisher
Elsevier
Research Rank
Q1
Research Vol
112
Research Website
https://doi.org/10.1016/j.bioorg.2021.104960
Research Year
2021
Research Member
Bahaa Gamal Al-Din Mohammad Yousef
Research_Pages
104960
Research Abstract

New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been
designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results
showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17–19 showed superior antiproliferative
activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed
promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19
increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19
demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of
EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.