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

See all articles by Ozair Alam

Ozair Alam

Medicinal Chemistry and Molecular Modelling Lab, Dept. of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062

Farah Nawaz

Jamia Hamdard (Hamdard University)

Date Written: February 19, 2020

Abstract

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

Suggested Citation

Alam, Ozair and Nawaz, Farah, 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 (February 19, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3541018

Ozair Alam (Contact Author)

Medicinal Chemistry and Molecular Modelling Lab, Dept. of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062 ( email )

TUGHLAQABAD INSTITUTIONAL AREA
HAMDARD NAGAR
DELHI, DE DELHI 110062
India

HOME PAGE: http://www.jamiahamdard.ac.in

Farah Nawaz

Jamia Hamdard (Hamdard University) ( email )

New Delhi
India

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