Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents

Shoman, Mai; Soltan, Osama; Nagaoka, Kieta; Abdel-aziz, Salah; Narumi, Atsushi; Konno, Hiroyuki; Abdelaziz, Mohamed

doi:10.21608/jabps.2021.73962.1127

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents

Document Type : Original Article

Authors

¹ Faculty of Pharmacy, Minia University, Minia Egypt

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt

³ Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan

⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt

⁵ Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan

10.21608/jabps.2021.73962.1127

Abstract

A series of new 1,5-diarylpyrazole carboxamide derivatives was designed and synthesized. All the synthesized compounds were biologically evaluated for their in vitro cytotoxic activities against a panel of five cancer cell lines namely, DLD, Hela, K-562, SUIT and HepG-2. The results revealed that compound 5c exhibited the most prominent cytotoxic effect against four tested cell lines with growth inhibition percentages ranged from 75.95 to 123 % and IC50 values of 17.20 and 21.20 μM comparable to that of daunorubicin as a control drug (IC50 values of 13.30 and 22 μM) against K-562 and Hep-G2 cell lines. Molecular docking study suggested the ability of the tested compounds to inhibit EGFR-TK. Data showed that 5c posses the ability to bind to erlotinib binding site forming a stable complex with energy scores -7.73 compared to -7.63 for erlotinib. It potentially forms three hydrogen bonds with LYS 721 and GLU 638 residues. Data suggests that compound 5c is a promising lead in the design of further EGFR inhibitors.

Keywords