الفهرس 
Title: Design and synthesis of new quinoline derivatives as chemotherapeutic agents
ContantsOnly 14 pages are availabe for public view
 |  | from | 197 |  |  |
| | | from | 197 | | |
Abstract
In the current study, we designed and synthesized novel quinoline derivatives as chemotherapeutic agents targeting cancer through the inhibition of VEGFR-2 activity. All compounds were tested for their VEGFR-2 inhibitory activity showing IC50 ranging from 36nM to 2.226μM compared to sorafenib as a reference drug with IC50= 45nM. Derivatives 10i and 10o were found to be the most potent derivatives with IC50 = 36nM and 38nM, respectively. All the synthesized derivatives were in vitro evaluated for their cytotoxic activity against HepG2 tumor cell line. Seven compounds 10a, 10c, 10d, 10e, 10i, 10n and 10o (IC50 = 4.60, 4.14, 1.07, 0.88, 2.76, 2.88 and 1.60μM respectively) displayed better antiproliferative activity than sorafenib (IC50= 8.38μM). The most potent compounds 10i and 10o were subjected to cytotoxicity screening against Transformed Human Liver Epithelial-2 normal cell line (THLE-2) to calculate their selectivity index. Additionally, we ran molecular docking studies to fit the designed derivatives into the binding site of the vascular endothelial growth factor receptor-2 (PDB code: 4ASD) to predict their probable binding interactions within the active site. Results indicated that compounds 10i and10o have probable to be used as lead compounds for the development of novel anticancer agents