Premium
Design, synthesis, molecular docking, anticancer evaluations, and in silico pharmacokinetic studies of novel 5‐[(4‐chloro/2,4‐dichloro)benzylidene]thiazolidine‐2,4‐dione derivatives as VEGFR‐2 inhibitors
Author(s) -
ElAdl Khaled,
ElHelby AbdelGhany A.,
Sakr Helmy,
Ayyad Rezk R.,
Mahdy Hazem A.,
Nasser Mohamed,
Abulkhair Hamada S.,
ElHddad Sanadelaslam S. A.
Publication year - 2021
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.202000279
Subject(s) - chemistry , sorafenib , cell culture , thiazolidine , doxorubicin , stereochemistry , cytotoxicity , docking (animal) , cancer cell , pharmacology , biochemistry , in vitro , cancer , cancer research , chemotherapy , biology , medicine , genetics , hepatocellular carcinoma , nursing
The anticancer activity of novel thiazolidine‐2,4‐diones was evaluated against HepG2, HCT‐116, and MCF‐7 cells. MCF‐7 was the most sensitive cell line to the cytotoxicity of the new derivatives. In particular, compounds 18 , 12 , 17 , and 16 were found to be the most potent derivatives over all the tested compounds against the cancer cell lines HepG2, HCT116, and MCF‐7, with IC 50 = 9.16 ± 0.9, 8.98 ± 0.7, 5.49 ± 0.5 µM; 9.19 ± 0.5, 8.40 ± 0.7, 6.10 ± 0.4 µM; 10.78 ± 1.2, 8.87 ± 1.5, 7.08 ± 1.6 µM; and 10.87 ± 0.8, 9.05 ± 0.7, 7.32 ± 0.4 µM, respectively. Compounds 18 and 12 have nearly the same activities as sorafenib (IC 50 = 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively), against HepG2 cells, but slightly lower activity against HCT116 cells and slightly higher activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against HepG2 and HCT‐116 cells but higher activity against MCF‐7 cells (IC 50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively). In contrast, compounds 17 and 16 exhibited lower activities than sorafenib against HepG2 and HCT116 cells, but nearly equipotent activity against the MCF‐7 cancer cell line. Also, these compounds displayed lower activities than doxorubicin against the three cell lines. All the synthesized derivatives 7 – 18 were evaluated for their inhibitory activities against VEGFR‐2. The tested compounds displayed high to medium inhibitory activity, with IC 50 values ranging from 0.17 ± 0.02 to 0.27 ± 0.03 µM. Compounds 18 , 12 , 17 , and 16 potently inhibited VEGFR‐2 at IC 50 values of 0.17 ± 0.02, 0.17 ± 0.02, 0.18 ± 0.02, and 0.18 ± 0.02 µM, respectively, which are nearly more than half of that of the IC 50 value for sorafenib (0.10 ± 0.02 µM).