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5-(4-Methoxybenzylidene)thiazolidine-2,4-dione-derived VEGFR-2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations.
- Source :
-
Archiv der Pharmazie [Arch Pharm (Weinheim)] 2020 Sep; Vol. 353 (9), pp. e2000079. Date of Electronic Publication: 2020 Jun 09. - Publication Year :
- 2020
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Abstract
- A novel series of 5-(4-methoxybenzylidene)thiazolidine-2,4-dione derivatives, 5a-g and 7a-f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF-7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF-7 cancer cell lines. Compound 7f (IC <subscript>50</subscript> = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively) exhibited a higher activity than sorafenib (IC <subscript>50</subscript> = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 µM, respectively) against HepG2 and MCF-7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC <subscript>50</subscript> = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively) against HepG2 and MCF-7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a-g and 7a-f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor-2 (VEGFR-2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR-2 at an IC <subscript>50</subscript> value of 0.12 ± 0.02 µM, which is nearly the same as that of sorafenib (IC <subscript>50</subscript> = 0.10 ± 0.02 µM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC <subscript>50</subscript> values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 µM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR-2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.<br /> (© 2020 Deutsche Pharmazeutische Gesellschaft.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Doxorubicin pharmacology
HCT116 Cells
Hep G2 Cells
Humans
Inhibitory Concentration 50
MCF-7 Cells
Molecular Docking Simulation
Neoplasms drug therapy
Neoplasms pathology
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Protein Kinase Inhibitors pharmacology
Sorafenib pharmacology
Structure-Activity Relationship
Thiazolidinediones chemical synthesis
Thiazolidinediones chemistry
Antineoplastic Agents pharmacology
Thiazolidinediones pharmacology
Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4184
- Volume :
- 353
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Archiv der Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 32515896
- Full Text :
- https://doi.org/10.1002/ardp.202000079