In Silico Design, Synthesis and Anticancer Activity of 3′-(4-(Benzyloxy)phenyl)-1′-Phenyl-5-(Pyridin-4-Yl)-3,4-Dihydro-1’H, 2H-3,4′-Bipyrazole as Potential EGFR Kinase Inhibitors
Posted: 23 Feb 2020
Date Written: February 19, 2020
A novel series of 3'-(4-(benzyloxy)phenyl)-1'-phenyl-5-(pyridin-4-yl)-3,4-dihydro-1'H,2H-3,4'-bipyrazole derivatives was designed, synthesized and evaluated its EGFR kinase inhibitory as well as antiproliferative activities against human cancer cell lines viz. MCF-7 (breast cancer), A549 (non-small lung tumour), HCT-116 (colon cancer) and SiHa (cancerous tissues of the cervix uteri). Compound 6f inhibits EGFR kinase at a concentration of 2.05µM. It was observed that among all synthesized compounds 6f showed most potent antiproliferative results against A549 cancer cell line having IC50 = 5.6 µM. Furthermore, compound 6f also induced apoptosis cancer cells as evident by DAPI staining and phase contrast microscopy. Potency to induce apoptosis by compound 6f was further confirmed by FACS using Annexin-V-FITC & propidium iodide (PI) labelling. Results of molecular docking studies suggested that compound 6f can binds to the hinge region of ATP binding site of EGFR Kinase like that of standard drug erlotinib. Hence, current study propose that compound 6f has potent in vitro antitumor activities against human non-small lung tumour cell line A549, which can be facilitated the research in other cancer cell lines and animal studies.
Keywords: EGFR, ANTICANCER, ANTIPROLIFERATIVE
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