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Design, Synthesis, and Cytotoxic Evaluation of Certain 7‐Chloro‐4‐(piperazin‐1‐yl)quinoline Derivatives as VEGFR‐II Inhibitors
Author(s) -
AboulEnein Mohamed Nabil,
ElAzzouny Aida M. Abd ElSattar,
Ragab Fatma AbdelFattah,
Hamissa Mohamed Farouk
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600377
Subject(s) - quinoline , chemistry , vegf receptors , cytotoxic t cell , pharmacology , cytotoxicity , stereochemistry , combinatorial chemistry , in vitro , cancer research , organic chemistry , biochemistry , biology
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, 1 H‐NMR, 13 C‐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 IC 50 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 IC 50 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.