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, Pages 214-225 PDF (1.03 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/jabps.2021.77469.1129 | ||
| Authors | ||
| Heba Hassan* 1; Kamal Abdelrahman2; Salah Abdel-aziz3; Adel Marzouk2; Hiroyuki Konno4; 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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