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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.
- Source :
-
Archiv der Pharmazie [Arch Pharm (Weinheim)] 2021 Feb; Vol. 354 (2), pp. e2000279. Date of Electronic Publication: 2020 Oct 19. - Publication Year :
- 2021
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Abstract
- 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 <subscript>50</subscript> = 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 <subscript>50</subscript> = 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 <subscript>50</subscript> = 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 <subscript>50</subscript> 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 <subscript>50</subscript> 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 <subscript>50</subscript> value for sorafenib (0.10 ± 0.02 µM).<br /> (© 2020 Deutsche Pharmazeutische Gesellschaft.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Structure-Activity Relationship
Thiazolidinediones chemical synthesis
Thiazolidinediones chemistry
Vascular Endothelial Growth Factor Receptor-2 metabolism
Antineoplastic Agents pharmacology
Drug Design
Molecular Docking Simulation
Protein Kinase Inhibitors pharmacology
Thiazolidinediones pharmacology
Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4184
- Volume :
- 354
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archiv der Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 33073374
- Full Text :
- https://doi.org/10.1002/ardp.202000279