Novel fluorinated pyrazole-based heterocycles scaffold: cytotoxicity, in silico studies and molecular modelling targeting double mutant EGFR L858R/T790M as antiproliferative and apoptotic agents

Abstract Hepatocellular carcinoma (HCC), also known as hepatoma, is the most prevalent type of primary liver cancer. It begins in hepatocytes, liver’s major cell type. Cancer that began another region body but has spread to secondary cancer life; several still unmet demands for better, less toxic therapy treat this malignant tumor. Several novel pyrazolo[1,5- a ]pyrimidine derivatives were synthesized part our goal develop promising anticancer drugs. All hybrids have been screened their cytotoxicity effect against three lines which are; HepG-2, HCT-116, and MCF-7. The cells found be sensitive new molecules. A subsequent set vitro biological evaluation studies conducted on identify such In HepG-2 cells, four ( 8a , 8b 10c 11b ) demonstrated good activity. efficacious compounds had IC 50 values 2.36 ± 0.14 1.14 0.063 μM, respectively, higher than reference medication Imatinib. latter’s putative molecular investigated further by looking at its influence cycle, EGFR, specific apoptotic anti-apoptotic markers cells. These findings indicated could trigger apoptosis upregulating BAX caspase-3 cycle Pre-G1 G2-M stages. showed high potency EGFR with equal 0.098 0.079 respectively. Compound effective inhibitory activity L858R-TK (36.79 nM). Additionally, silico ADMET docking done active hits, representing results. Graphical