Junaid Ahmad, Lim Felicia Phei Lin, Chuah Lay Hong, Dolzhenko Anton V
School of Pharmacy, Monash University Malaysia Jalan Lagoon Selatan Bandar Sunway Selangor Darul Ehsan 47500 Malaysia
School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University GPO Box U1987 Perth Western Australia 6845 Australia.
RSC Adv. 2020 Mar 25;10(21):12135-12144. doi: 10.1039/d0ra00643b. eCollection 2020 Mar 24.
A library of 126 compounds with a 6, -diaryl-1,3,5-triazine-2,4-diamine scaffold was prepared using a one-pot, microwave-assisted method from readily available cyanoguanidine, aromatic aldehydes and arylamines. The three-component condensation of these reagents in the presence of hydrochloric acid was followed by the treatment with a base, which promoted a rearrangement of the dihydrotriazine ring and its dehydrogenative aromatization. The antiproliferative properties of the prepared compounds were evaluated using three breast cancer cell lines. The most promising results were obtained in the growth inhibition of the triple negative MDA-MB231 breast cancer cells. The active compounds were also selective against cancer cells and did not affect growth of the non-cancerous MCF-10A breast cell line. Analyzing the structure-activity relationship within the series, we built a 3D-QSAR model for the further design of more potent anticancer compounds.
使用一锅法微波辅助方法，以易得的氰基胍、芳香醛和芳胺为原料，制备了一个包含126种具有6, -二芳基-1,3,5-三嗪-2,4-二胺骨架的化合物库。这些试剂在盐酸存在下进行三组分缩合反应，随后用碱处理，碱促进了二氢三嗪环的重排及其脱氢芳构化。使用三种乳腺癌细胞系评估了所制备化合物的抗增殖特性。在三阴性MDA-MB231乳腺癌细胞的生长抑制方面获得了最有前景的结果。活性化合物对癌细胞也具有选择性，不影响非癌性MCF-10A乳腺细胞系的生长。通过分析该系列中的构效关系，我们构建了一个3D-QSAR模型，用于进一步设计更有效的抗癌化合物。
