Chaudhary Chhabi Lal, Ko Seungyun, Lee Chaerim, Kim Yerin, Jung Chanhyun, Hyun Soonsil, Kwon Youngjoo, Kang Jong-Soon, Jung Jae-Kyung, Lee Heesoon
College of Pharmacy and Medicinal Research Center (MRC), Chungbuk National University, Cheongju 28160, Korea.
College of Pharmacy, Ewha Womans University, Seoul 03760, Korea.
Pharmaceuticals (Basel). 2022 Mar 24;15(4):399. doi: 10.3390/ph15040399.
With the several targets of cancer treatment, inhibition of DNA topoisomerase activity is one of the well-known focuses in cancer chemotherapy. Here, we describe the design and synthesis of a novel series of pyrazolo[4,3-]quinolines with potential anticancer/topoisomerase inhibition activity. Forty newly designed pyrazolo[4,3-]quinoline derivatives were synthesized via inverse imino Diels-Alder reaction. The antiproliferative activity of the synthesized derivatives was initially measured in the human NUGC-3 cancer cell line. Then, the selected compounds , , , , , , , and with higher activity among tested compounds were screened against six cancer cell lines, including ACHN, HCT-15, MM231, NCI-H23, NUGC-3, and PC-3. The results demonstrated that the compounds , , and were most effective in all cancer cell lines exhibiting GI below 8 µM. Among them, showed an equivalent inhibition pattern of topoisomerase IIα activity to that of etoposide, positive control at a 100 µM dose.
随着癌症治疗的多个靶点，抑制DNA拓扑异构酶活性是癌症化疗中一个众所周知的重点。在此，我们描述了一系列具有潜在抗癌/拓扑异构酶抑制活性的新型吡唑并[4,3 - ]喹啉的设计与合成。通过逆亚氨基狄尔斯-阿尔德反应合成了40种新设计的吡唑并[4,3 - ]喹啉衍生物。首先在人NUGC - 3癌细胞系中测定合成衍生物的抗增殖活性。然后，在包括ACHN、HCT - 15、MM231、NCI - H23、NUGC - 3和PC - 3在内的六种癌细胞系中筛选测试化合物中活性较高的所选化合物 、 、 、 、 、 、 和 。结果表明，化合物 、 和 在所有癌细胞系中最为有效，其生长抑制率低于8 µM。其中， 在100 µM剂量下对拓扑异构酶IIα活性的抑制模式与阳性对照依托泊苷相当。
