Design, synthesis, and molecular docking of novel indole scaffold‐based VEGFR‐2 inhibitors as targeted anticancer agents. Issue 2 (11th January 2018)

• Record Type: Journal Article
• Authors: Roaiah, Hanaa M.; Ghannam, Iman A. Y.; Ali, Islam H.; El Kerdawy, Ahmed M.; Ali, Mamdouh M.; Abbas, Safinaz E‐S.; El‐Nakkady, Sally S.
• Is Part Of: Archiv der Pharmazie. Volume 351:Issue 2(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-01-11
• Subjects: anticancer agents -- indole -- molecular docking -- VEGFR‐2 inhibitors; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201700299
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: A series of new indole derivatives1 –18 was synthesized and tested for their cytotoxic activity on a panel of 60 tumor cell lines. Additionally, molecular docking was carried out to study their binding pattern and binding affinity in the VEGFR‐2 active site using sorafenib as a reference VEGFR‐2 inhibitor. Based on the molecular docking results, compounds5a, 5b, 6, 7, 14b, 18b, and18c were selected to be evaluated for their VEGFR‐2 inhibitory activity. Compound18b exhibited a broad‐spectrum antiproliferative activity on 47 cell lines, with GI % ranging from 31 to 82.5%. Moreover, compound18b was the most potent VEGFR‐2 inhibitor with an IC50 value of 0.07 μM, which is more potent than that of sorafenib (0.09 μM). A molecular docking study attributed the promising activity of this series to their hydrophobic interaction with the VEGFR‐2 binding site hydrophobic side chains and their hydrogen bonding interaction with the key amino acids Glu885 and/or Asp1046. Abstract : A series of new indole derivatives1–18 were synthesized and tested for their cytotoxic activity on a panel of tumor cell lines. Compound18b showed broad‐spectrum anti‐proliferative activity on 47 cell lines and was also the most potent VEGFR‐2 inhibitor (IC50 = 0.07 vs. 0.09 µM of sorafenib). Molecular docking was carried out to study the binding pattern and binding affinity in the VEGFR‐2 active site.