Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents
Shoman, M., soltan, O., Nagaoka, K., Abdel-aziz, S., Narumi, A., Konno, H., Abdelaziz, M. (2021). Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents. EKB Journal Management System, 4(3), 152-159. doi: 10.21608/jabps.2021.73962.1127
Mai Shoman; osama soltan; kieta Nagaoka; Salah Abdel-aziz; Atsushi Narumi; Hiroyuki Konno; Mohamed Abdelaziz. "Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents". EKB Journal Management System, 4, 3, 2021, 152-159. doi: 10.21608/jabps.2021.73962.1127
Shoman, M., soltan, O., Nagaoka, K., Abdel-aziz, S., Narumi, A., Konno, H., Abdelaziz, M. (2021). 'Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents', EKB Journal Management System, 4(3), pp. 152-159. doi: 10.21608/jabps.2021.73962.1127
Shoman, M., soltan, O., Nagaoka, K., Abdel-aziz, S., Narumi, A., Konno, H., Abdelaziz, M. Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents. EKB Journal Management System, 2021; 4(3): 152-159. doi: 10.21608/jabps.2021.73962.1127

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

Journal of Advanced Biomedical and Pharmaceutical Sciences
Article 4, Volume 4, Issue 3, July 2021, Pages 152-159    PDF (750.01 K)
Document Type: Original Article
DOI: 10.21608/jabps.2021.73962.1127
Authors
Mai Shoman* 1; osama soltan2; kieta Nagaoka3; Salah Abdel-aziz4; Atsushi Narumi5; Hiroyuki Konno3; Mohamed Abdelaziz1
1Faculty of Pharmacy, Minia University, Minia Egypt
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
3Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan
4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt
5Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan
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
Anticancer; 1; 5-diarylpyrazole derivatives; EGFR-TKI; Molecular docking
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