Design, Synthesis, and Cytotoxic Evaluation of Certain 7 ‐Chloro‐4‐(piperazin‐1‐yl)quinoline Derivatives as VEGFR‐II Inhibitors

Signaling pathway inhibition of VEGFR‐II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1‐4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)‐2‐(N‐substituted‐amino)‐ethanone derivatives (4a–t) was achieved through the amination of 2‐chloro‐1‐(4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, 1H‐NMR, 13C‐NMR, HRMS, and microanalysis. Compounds 4a–t were subjected to in vitro anticancer screening against human breast cancer (MCF‐7) and prostate cancer (PC3) cell lines. The highest cytotoxicty against both cell lines was displayed by 2‐(4‐(4‐bromobenzyl)piperazin‐1‐yl)‐1‐(4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)ethanone (4q), with IC50 values of 6.502 and 11.751 μM against MCF‐7 and PC3 cells, respectively, compared with the standard drug doxorubicin (MCF‐7: 6.774 μM, PC3: 7.7316 μM). Due to its notable activity toward MCF‐7 cells, 4q was further evaluated as VEGFR‐II inhibitor, showing an IC50 of 1.38 μM compared to sorafenib (0.33 μM). The docking study proved that 4q has a binding mode akin to that of VEGFR‐II inhibitors. Novel 1‐4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)‐2‐(N‐substituted‐amino)ethanone derivatives (4a–t) were synthesized and evaluated against the human breast cancer cell line MCF‐7. Due to its n...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research