Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers

Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Percentage inhibition in 14 human cancer cell lines and IC values were recorded. Compounds , and were examined against both wild and mut...

Full description

Saved in:
Bibliographic Details
Published in:Future medicinal chemistry 2023-10, Vol.15 (19), p.1773-1790
Main Authors: Gaber, Ahmed A, Sharaky, Marwa, Elmaaty, Ayman Abo, Hammouda, Mohamed M, Mourad, Ahmed AE, Elkhawaga, Samy Y, Mokhtar, Mahmoud Mohamed, Abouzied, Amr S, Mourad, Mai AE, Al-Karmalawy, Ahmed A
Format: Article
Language:English
Subjects:
apoptosis markers
EGFR TKIs
EGFR-T790M
EGFR-WT
pyrazolopyrimidine
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:Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Percentage inhibition in 14 human cancer cell lines and IC values were recorded. Compounds , and were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Compounds , and demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds and had the best fit. The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2023-0156