Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.
Hassan, H., Abdelrahman, K., Abdel-aziz, S., Marzouk, A., Konno, H., Tajiri, M., Osman, M., shams, R. (2021). Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.. EKB Journal Management System, 4(4), 214-225. doi: 10.21608/jabps.2021.77469.1129
Heba Hassan; Kamal Abdelrahman; Salah Abdel-aziz; Adel Marzouk; Hiroyuki Konno; Misato Tajiri; Mohamed Osman; raef shams. "Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.". EKB Journal Management System, 4, 4, 2021, 214-225. doi: 10.21608/jabps.2021.77469.1129
Hassan, H., Abdelrahman, K., Abdel-aziz, S., Marzouk, A., Konno, H., Tajiri, M., Osman, M., shams, R. (2021). 'Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.', EKB Journal Management System, 4(4), pp. 214-225. doi: 10.21608/jabps.2021.77469.1129
Hassan, H., Abdelrahman, K., Abdel-aziz, S., Marzouk, A., Konno, H., Tajiri, M., Osman, M., shams, R. Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.. EKB Journal Management System, 2021; 4(4): 214-225. doi: 10.21608/jabps.2021.77469.1129

Design, synthesis, molecular docking and biological evaluation of novel 1,5-diarylpyrazole-N,O-dimethyl hydroxamate derivatives as antiproliferative agents.

Journal of Advanced Biomedical and Pharmaceutical Sciences
Article 3, Volume 4, Issue 4, October 2021, Page 214-225  XML PDF (1.03 MB)
Document Type: Original Article
DOI: 10.21608/jabps.2021.77469.1129
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Authors
Heba Hassan email 1; Kamal Abdelrahman2; Salah Abdel-aziz3; Adel Marzouk2; Hiroyuki Konnoorcid 4; Misato Tajiri5; Mohamed Osman6; raef shams7
1Med Chem Dept, Faculty of Pharmacy, Minia Uiversity
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut
3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt
4Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan
5Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan
6Medicinal Chemistry Department, Faculty of Pharmacy, Minia University.
7Emergent Bioengineering Materials Research Team, RIKEN Centre for Emergent Matter Science, RIKEN, Wako, Saitama 351-0198, Japan.
Abstract
A series of novel hybrid of 1,5-diarylpyrazole-N,O-dimethylhydroxamate derivatives were designed and synthesised in synthetically acceptable yields. All the new synthesized compounds were biologically evaluated for their in vitro cytotoxicity against a panel of five cell lines namely human colorectal adenocarcinoma cell line DLD1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cancer cell line Suit-2 and human hepatocellular carcinoma cell line HepG2. Compound 7a showed a significant cytotoxicity against Hela cell line with IC50 value of 16 µM and a good cytotoxicity against DLD1 and HepG2 with IC50 values of 69.9 µM and 78.8µM. Also, compound 7a displayed a potent EGFR inhibitory activity with IC50= 4.00 µM, which was comparable to positive reference drug sorafenib (IC50 = 3.5 µM). Moreover, in-silico studies showed that compound 7a has excellent binding affinity to the active site of EGFR with binding score better than a multitarget kinase drug sorafenib and good binding affinity to JNK-2, which explains the anticancer activity of compound 7a.
Keywords
Pyrazole; hydroxamate; Cancer; EGFR
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