| Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties |
| Paper ID : 1062-ISCH |
| Authors |
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Dalia Raslan Aboshouk *1, mohammed adel mohammed Youssef2, adel s. girgis3 1Assistant researcher, Department of Pesticide Chemistry, National Research Centre 2Department of Chemistry, Faculty of Science, Helwan University, Helwan, Egypt 3Department of Pesticide Chemistry, National Research Centre |
| Abstract |
| Cancer is still one of the most challenging diseases globally. Targeted therapy has gained a lot of interest recently due to efficient therapeutic potential and fewer side effects. The current study is directed towards design and synthesis of a set of 2-oxoindolin-3-ylidenes incorporating urea function attempting to optimize potent VEGFR-2 inhibitors utilizing pharmacophoric units of sunitinib and sorafenib (approved anticancer drugs). The targeted agents were synthesized through a two-step reaction. Addition of the appropriate 1-(acetylphenyl)-3-phenylureas to the corresponding isatins in ethanol containing a quantitative amount of Et2NH followed by acidic dehydration (AcOH/HCl) afforded the targeted agents. Promising antiproliferative properties (MTT assay) were noticed by the synthesized agents against HCT116, MCF7 and PaCa2 cancer cell lines relative to standard reference (sunitinib) with safe behavior against non-cancer (RPE1) cell line. VEGFR2 inhibitory effect was evidenced by some of the synthesized agents with comparable activity to that of sunitinib. Molecular docking studies (PDB: 3WZE and 3AGD) support the bio-observations. |
| Keywords |
| Cancer, 2-Oxoindolin-3-ylidenes, VEGFR-2, Molecular modeling |
| Status: Abstract Accepted (Poster Presentation) |