Kaya-Sezginer Ecem, Oz Bedir Beyza Ecem, Terzi Emine, Ozdemir Sanci Tuba, Maryam Zahra, Acar Çevik Ulviye
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Türkiye.
Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Türkiye.
Chem Biol Drug Des. 2024 Dec;104(6):e70033. doi: 10.1111/cbdd.70033.
New series of benzimidazole-1,2,4-triazole derivatives were designed, synthesized, and characterized using H-NMR, C-NMR, and HRMS. These compounds were evaluated for anticancer activity toward HTB-9 bladder and HT-29 colorectal cancer cell lines. Compounds 7h and 7ı were found to be the most active against HTB-9 cell line, with IC 6.27 and 6.44 μM, respectively, comparable to positive control cisplatin (IC = 11.40 μM). Additionally, in HT-29 cell line, compounds 7a and 7ı exhibited the lowest IC values (20.37 and 22.71 μM, respectively), which was higher than those of cisplatin (19.79 μM). All active compounds induced apoptosis and caspase 3/7 activity and reduced the migration ability in both cell lines. Particularly, HT-29 cells treated with compound 7ı exerted a higher apoptotic index than cisplatin-treated cells. Furthermore, compounds 7h and 7ı led to G1 cell cycle arrest of HTB-9, and compounds 7a and 7ı against HT-29 induced S and G1 cell cycle arrest, respectively. In conclusion, the antiproliferative effect of active compounds is associated with the induction of apoptosis through caspase 3/7 activation and cell cycle arrest at different phases in HTB-9 and HT-29 cell lines.
设计、合成了一系列新的苯并咪唑 -1,2,4 - 三唑衍生物，并利用氢核磁共振（H-NMR）、碳核磁共振（C-NMR）和高分辨质谱（HRMS）对其进行了表征。评估了这些化合物对HTB - 9膀胱癌细胞系和HT - 29结肠癌细胞系的抗癌活性。发现化合物7h和7ı对HTB - 9细胞系活性最高，其半数抑制浓度（IC）分别为6.27和6.44 μM，与阳性对照顺铂（IC = 11.40 μM）相当。此外，在HT - 29细胞系中，化合物7a和7ı表现出最低的IC值（分别为20.37和22.71 μM），高于顺铂（19.79 μM）。所有活性化合物均诱导细胞凋亡和半胱天冬酶3/7活性，并降低了两种细胞系的迁移能力。特别是，用化合物7ı处理的HT - 29细胞的凋亡指数高于顺铂处理的细胞。此外，化合物7h和7ı导致HTB - 9细胞的G1期细胞周期阻滞，而针对HT - 29的化合物7a和7ı分别诱导S期和G1期细胞周期阻滞。总之，活性化合物的抗增殖作用与通过激活半胱天冬酶3/7诱导细胞凋亡以及在HTB - 9和HT - 29细胞系的不同阶段使细胞周期阻滞有关。
