Patel Mrugesh, Pandey Nilesh, Timaniya Jignesh, Parikh Paranjay, Chauhan Alex, Jain Neeraj, Patel Kaushal
Department of Advanced Organic Chemistry, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology Gujarat 388421 India
Department of Medical Laboratory Technology, Charotar Institute of Paramedical Sciences, Charotar University of Science and Technology Gujarat 388421 India
RSC Adv. 2021 Aug 13;11(44):27627-27644. doi: 10.1039/d1ra03970a. eCollection 2021 Aug 9.
A series of novel pyrazoline scaffolds from coumarin-carbazole chalcones were synthesized. We explored various acetyl, amide, and phenyl substituents at the -1 position of the pyrazoline core. The synthesized compounds were characterized by FTIR, H-NMR, C-NMR, DEPT, and mass spectroscopic techniques. The cytotoxicity study of all the synthesized compounds was evaluated against HeLa, NCI-H520 and NRK-52E cell lines. Compounds 4a and 7b became the most active compounds and exhibited their potential to arrest the cell cycle progression and induce apoptosis in both the cell lines. In addition, molecular docking studies revealed a higher binding affinity of both the molecules with CDK2 protein. Based on the obtained results, a comprehensive analysis is warranted to establish the role of compounds 4a and 7b as promising cancer therapeutic agents.
合成了一系列基于香豆素 - 咔唑查尔酮的新型吡唑啉支架。我们在吡唑啉核心的 -1 位探索了各种乙酰基、酰胺基和苯基取代基。通过傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、无畸变极化转移增强法（DEPT）和质谱技术对合成的化合物进行了表征。对所有合成化合物针对人宫颈癌HeLa细胞系、人非小细胞肺癌NCI-H520细胞系和大鼠肾细胞NRK-52E细胞系进行了细胞毒性研究。化合物4a和7b成为活性最高的化合物，并显示出在两个细胞系中阻滞细胞周期进程和诱导细胞凋亡的潜力。此外，分子对接研究表明这两种分子与细胞周期蛋白依赖性激酶2（CDK2）蛋白具有更高的结合亲和力。基于所获得的结果，有必要进行全面分析以确定化合物4a和7b作为有前景的癌症治疗药物的作用。
