New Coumarin Derivatives as Anti‐Breast and Anti‐Cervical Cancer Agents Targeting VEGFR‐2 and p38α MAPK. Issue 9 (8th August 2017)

• Record Type: Journal Article
• Authors: Batran, Rasha Z.; Dawood, Dina H.; El‐Seginy, Samia A.; Ali, Mamdouh M.; Maher, Timothy J.; Gugnani, Kuljeet S.; Rondon‐Ortiz, Alejandro N.
• Is Part Of: Archiv der Pharmazie. Volume 350:Issue 9(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-08-08
• Subjects: Breast cancer -- Cervical cancer -- Fluorinated coumarins -- Molecular modeling -- p38α MAPK -- QSAR -- VEGFR‐2; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201700064
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : Breast and cervical cancers are the most common gender‐specific cancers affecting women worldwide. In this investigation, we highlighted the synthesis, VEGFR‐2 and p38α MAPK inhibitory activity of new series of fluorinated coumarin‐based derivatives featuring a variety of bioactive chemical moieties attached or fused to the coumarin nucleus at the 3 and/or 4 position. The bioactive inhibitors were further assessed for their anti‐proliferative effect against human MCF‐7 breast cancer and HeLa cervical cancer cell lines, respectively. Most of the tested compounds showed potent preferential inhibition effects against human VEGFR‐2 and remarkable anticancer activities in the human breast cancer cell line MCF‐7. Compounds29, 24, and2 displayed the highest inhibitory activity against VEGFR‐2 (94% inhibition) and they were the most potent anticancer agents toward MCF‐7 cancer cells with IC50 values of 7.90, 8.28, and 8.30 μg/mL, respectively. Compound13 inhibited p38α MAPK phosphorylation with a significant reduction in % cell viability against HeLa cancer cells at 10 and 30 µM. Docking experiments carried out on VEGFR‐2 and p38 MAPK crystallographic structures revealed that the active compounds bind to the active sites through H‐bonds, arene–cation, and hydrophobic π–π interactions. QSAR analysis demonstrated considerable correlation coefficient ( R 2 = 0.76969) and root mean square error (RMSE = 0.10446) values. Also, the residual values between the experimental pIC50 and predicted pIC50 are very close, indicating the reliability of the established QSAR model. Abstract : The VEGFR‐2 and p38α MAPK inhibitory activities of new series of fluorinated coumarin‐based derivatives with bioactive chemical moieties attached or fused to the coumarin nucleus at the 3 and/or 4 position are explored. Compounds29, 24, and2 displayed the highest inhibitory activity against VEGFR‐2 (94% inhibition); they were also the most potent anticancer agents towards MCF‐7 cancer cells (IC50 = 7.90, 8.28, and 8.30 μg/mL, respectively).