Drug Res (Stuttg) 2021; 71(07): 388-394
DOI: 10.1055/a-1498-1714
Original Article

Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Bilqees Sameem
1  Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
,
Ebrahim Saeedian Moghadam
1  Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
2  Department of Chemistry, College of Science, Sultan Qaboos University, Muscat, Sultanate of Oman
,
Majid Darabi
1  Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
,
Zahra Shahsavari
3  Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Mohsen Amini
1  Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
› Author Affiliations
Funding: This work was financially supported by The National Institute for Medical Research Development (NIMAD), GN: 958948.

Abstract

Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important.

Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives.

Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated.

Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)- 1H-pyrazole were synthesized in good yields and their structure and purity were confirmed using 1H-NMR, 13C-NMR, and elemental analysis. Generally, the synthesized scaffolds exhibited good cytotoxicity against cancerous cell lines in comparison to the reference standard, paclitaxel. Compounds 3a and 3c, in Annexin V/ PI staining assay, exerted remarkable activity in apoptosis induction in HT-29 cell lines. Both of them also led to cell cycle arrest in the sub-G1 phase which is inconsistent with the results of apoptosis assay.

Conclusion Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.



Publication History

Received: 11 February 2021

Accepted: 30 April 2021

Publication Date:
19 May 2021 (online)

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