School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, PR China; Henan Qunbo Pharmaceutical Research Institute Co. LTD, Zhengzhou 450001, PR China.
Bioorg Med Chem Lett. 2022 May 15;64:128654. doi: 10.1016/j.bmcl.2022.128654. Epub 2022 Mar 5.
In this study, a novel batch of indazole containing 1,2,3-triazole agents were designed and synthesized. The antiproliferative activity of target compounds in four human cancer cells, PC-3 (human prostate cancer cell), MCF-7 (human breast cancer cell), HepG-2 (human hepatoma cell) and MGC-803 (human gastric cancer cell), was evaluated by thiazole blue (MTT). In the antiproliferative activity screening, we were surprised to find that most compounds have specific cytotoxicity to PC-3 cancer cells. In particular, 9a has an IC value of 4.42 ± 0.06 μmol/L against PC-3 cell. Cloning experiments showed that 9a could inhibit the formation of PC-3 cancer cell clone in a dose-dependent manner. Through cell cycle arrest experiment, we found that compound 9a can block the cell cycle in G2/M phase and inhibit cell proliferation. Finally, by evaluating the safety of compound 9a, we noticed that it showed fairly good safety both in vivo and in vitro. Overall, based on the biological activity evaluation and safety, analogue 9a can be viewed as a potential lead compound for further development of novel anti-prostate cancer drug.
在这项研究中，设计并合成了一批新型含吲唑的 1,2,3-三唑类化合物。采用噻唑蓝（MTT）法评估目标化合物对四种人癌细胞（PC-3、MCF-7、HepG-2 和 MGC-803）的增殖抑制活性。在增殖抑制活性筛选中，我们惊讶地发现大多数化合物对 PC-3 癌细胞具有特定的细胞毒性。特别是化合物 9a 对 PC-3 细胞的 IC 值为 4.42±0.06 μmol/L。克隆实验表明，9a 能以剂量依赖的方式抑制 PC-3 癌细胞克隆的形成。通过细胞周期阻滞实验，我们发现化合物 9a 可以将细胞周期阻滞在 G2/M 期，从而抑制细胞增殖。最后，通过评价化合物 9a 的安全性，我们注意到它在体内和体外均表现出相当好的安全性。总体而言，基于生物活性评价和安全性，类似物 9a 可以被视为进一步开发新型抗前列腺癌药物的潜在先导化合物。
