Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and In Vitro Cytotoxicity
Akram H Abd El-Haleem1, Manar Abd El-Karim Kassem1, Mohamed R Elnagar2,3
1Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Sixth of October City, Giza 77, Egypt.
Abstract:
New derivatives 4a-d, 6, 7a-d, 8a-c, 9, 11a, 11b, 12a-f, 13a-c, and 14 were synthesized and evaluated for their VEGFR-2 inhibition. Compounds 4c, 7b, and 7c showed remarkable enzyme inhibition (IC50 = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC50 = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 cancer cell lines in addition to WI-38. Compound 7b displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC50 = 6.66 and 8.51 μM) compared to sorafenib (IC50 = 6.60 and 8.78 μM). Cell cycle analysis and apoptotic assay of 7b in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of apoptosis. Western blot analysis of compound 7b revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of 7b showed inhibition of wound closure. Additionally, molecular modeling studies of compounds 4c, 7b, and 7c were carried out.
Related Concept Videos
Inhibition of Cdk Activity
Targeted Cancer Therapies
There are several types of targeted therapies against...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase


