Karthikeyan Chandrabose, Amawi Haneen, Viana Arabela Guedes, Sanglard Leticia, Hussein Noor, Saddler Maria, Ashby Charles R, Moorthy N S Hari Narayana, Trivedi Piyush, Tiwari Amit K
Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak 484887, India; School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462036, India.
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, OH, USA.
Bioorg Med Chem Lett. 2018 Jul 15;28(13):2244-2249. doi: 10.1016/j.bmcl.2018.05.045. Epub 2018 May 24.
A series of lH-pyrazolo[3,4-b]quinolin-3-amine derivatives were synthesized and evaluated for anticancer efficacy in a panel of ten cancer cell lines, including breast (MDAMB-231 and MCF-7), colon (HCT-116, HCT-15, HT-29 and LOVO), prostate (DU-145 and PC3), brain (LN-229), ovarian (A2780), and human embryonic kidney (HEK293) cells, a non-cancerous cell line. Among the eight derivatives screened, compound QTZ05 had the most potent and selective antitumor efficacy in the four colon cancer cell lines, with IC values ranging from 2.3 to 10.2 µM. Furthermore, QTZ05 inhibited colony formation in HCT-116 cells in a concentration-dependent manner. Cell cycle analysis data indicated that QTZ05 caused an arrest in the sub G1 cell cycle in HCT-116 cells. QTZ05 induced apoptosis in HCT-116 cells in a concentration-dependent manner that was characterized by chromatin condensation and increase in the fluorescence of fluorochrome-conjugated Annexin V. The findings from our study suggest that QTZ05 may be a valuable prototype for the development of chemotherapeutics targeting apoptotic pathways in colorectal cancer cells.
合成了一系列1H-吡唑并[3,4-b]喹啉-3-胺衍生物，并在包括乳腺癌（MDAMB-231和MCF-7）、结肠癌（HCT-116、HCT-15、HT-29和LOVO）、前列腺癌（DU-145和PC3）、脑癌（LN-229）、卵巢癌（A2780）以及人胚肾（HEK293）细胞（一种非癌细胞系）在内的十种癌细胞系中评估了其抗癌效果。在筛选的八种衍生物中，化合物QTZ05在四种结肠癌细胞系中具有最强且最具选择性的抗肿瘤效果，其IC值范围为2.3至10.2 μM。此外，QTZ05以浓度依赖性方式抑制HCT-116细胞中的集落形成。细胞周期分析数据表明，QTZ05导致HCT-116细胞的亚G1期细胞周期停滞。QTZ05以浓度依赖性方式诱导HCT-116细胞凋亡，其特征为染色质浓缩以及荧光素偶联膜联蛋白V荧光增加。我们的研究结果表明，QTZ05可能是开发针对结肠癌细胞凋亡途径的化疗药物的有价值的原型。
