新型取代咪唑-硫酮连接苯并三唑衍生物的设计、合成及抗增殖活性。

Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives.

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

出版信息

Molecules. 2021 Oct 2;26(19):5983. doi: 10.3390/molecules26195983.

DOI:10.3390/molecules26195983

PMID:34641526

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8512560/

Abstract

A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC 3.57, 0.40 and 2.63 µM, respectively. Compound was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G/M phase. Compound showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.

摘要

设计、合成并评价了一系列新型含取代咪唑-2-硫酮的苯并三唑部分的 N1 取代物，以评估其对 MCF-7（乳腺癌）、HL-60（人早幼粒细胞白血病）和 HCT-116（结肠癌）不同癌细胞系的体外抗癌活性。大多数苯并三唑类似物对测试的癌细胞系表现出有希望的增殖抑制活性。在所有合成的化合物中，化合物对 MCF-7、HL-60 和 HCT-116 等癌细胞系表现出较强的活性，IC 50 值分别为 3.57、0.40 和 2.63 μM。选择化合物进行详细的生物学研究，发现其能将 HL-60 细胞周期阻滞在 G/M 期。化合物能显著抑制微管蛋白聚合，并与微管蛋白的秋水仙碱结合位点结合。此外，化合物还通过调节促凋亡蛋白 BAX 和抗凋亡蛋白 Bcl-2 的表达来促进细胞凋亡。这些结果为进一步合理开发用于治疗癌症的强效微管蛋白聚合抑制剂提供了指导。