New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study

Two new series of oxadiazole and pyrazoline derivatives were designed and synthesized as promising EGFR-TK inhibitors. The in vitro antiproliferative activity was studied against three human cancer cell lines; HCT116, HepG-2 and MCF7 using MTT assay. Compound 10c showed the most potent anticancer ac...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2024-03, Vol.14 (1), p.5474-5474, Article 5474
Main Authors: Serag, Marwa I., Tawfik, Samar S., Badr, Sahar M. I., Eisa, Hassan M.
Format: Article
Language:English
Subjects:
631/67
639/638
Anticancer activity
Antitumor activity
Apoptosis
Cell Cycle
Docking studies
Doxorubicin
EGFR kinase
Epidermal growth factor receptors
ErbB Receptors
Gefitinib
Humanities and Social Sciences
Humans
Molecular Docking Simulation
multidisciplinary
Oxadiazole
Oxadiazoles - pharmacology
Physicochemical properties
Pyrazoline
Science
Science (multidisciplinary)
Tumor cell lines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two new series of oxadiazole and pyrazoline derivatives were designed and synthesized as promising EGFR-TK inhibitors. The in vitro antiproliferative activity was studied against three human cancer cell lines; HCT116, HepG-2 and MCF7 using MTT assay. Compound 10c showed the most potent anticancer activity against all cancer cell lines, with IC 50 range of 1.82 to 5.55 μM, while proving safe towards normal cells WI-38 (IC 50  = 41.17 μM) compared to the reference drug doxorubicin (IC 50  = 6.72 μM). The most active candidates 5a, 9b, 10a, 10b and 10c were further assessed for their EGFR-TK inhibition. The best of which, compounds 5a and 10b showed IC 50 of 0.09 and 0.16 μM respectively compared to gefitinib (IC 50  = 0.04 μM). Further investigation against other EGFR family members, showed that 5a displayed good activities against HER3 and HER4 with IC 50 values 0.18 and 0.37 µM, respectively compared to gefitinib (IC 50  = 0.35 and 0.58 µM, respectively). Furthermore, 5a was evaluated for cell cycle distribution and apoptotic induction on HepG-2 cells. It induced mitochondrial apoptotic pathway and increased accumulation of ROS. Molecular docking study came in agreement with the biological results. Compounds 5a and 10b showed promising drug-likeness with good physicochemical properties.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-55046-0