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.
Department of Chemistry, College of Science, Sultan Qaboos University, Muscat, Sultanate of Oman.
Drug Res (Stuttg). 2021 Sep;71(7):388-394. doi: 10.1055/a-1498-1714. Epub 2021 May 19.
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.
Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives.
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.
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 H-NMR, C-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.
Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.
近年来，有几种抗癌药物被引入用于治疗多种癌症。尽管它们在癌症治疗中有一定的潜力，但耐药性和周围神经病变等不良反应是抗癌药物的一些负面标准，因此，设计和合成新的抗癌药物非常重要。
设计、合成和评估一些吡唑衍生物的抗癌活性。
采用多步合成法合成了一系列目标化合物。采用体外 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法检测它们对三种不同的人癌细胞系（人结肠癌细胞（HT-29）、上皮癌细胞（U-87MG）、胰腺癌细胞（Panc-1））以及 AGO1522 正常细胞系的细胞毒性。
以较高的产率合成了 1,3-二芳基-5-(3,4,5-三甲氧基苯基)-4,5-二氢-1H-吡唑和 1,3-二芳基-5-(3,4,5-三甲氧基苯基)-1H-吡唑，并通过 1H-NMR、13C-NMR 和元素分析确认了它们的结构和纯度。一般来说，与参比标准紫杉醇相比，合成的支架对癌细胞系表现出良好的细胞毒性。在 Annexin V/PI 染色试验中，化合物 3A：和 3C：在 HT-29 细胞系中表现出显著的诱导细胞凋亡活性。它们还导致细胞周期在亚 G1 期停滞，这与凋亡试验的结果不一致。
鉴于所获得的结果，有兴趣合成更多的吡唑衍生物作为抗癌药物。
