title: Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking.
abstract: In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2-oxoindolin-3-ylidene)amino)phenyl)-3-arylureas was designed and synthesized. All the newly prepared ureas 9a-x were evaluated in vitro for their anti-proliferative activity against HepG2 hepatocellular carcinoma cell line. Compounds 9a-c, 9e, 9f, 9j, 9m-o, 9t-v and 9x exhibited good activity against HepG2 cancer cells (IC50 = 1.22 ± 0.11-8.37 ± 0.85 μM) comparable to that of doxorubicin and sorafinib (IC50 = 2.90 ± 0.36 and 3.40 ± 0.25 μM, respectively). These thirteen compounds were further evaluated for their inhibitory activity against VEGFR-2. Compound 9x emerged as the most active counterpart against VEGFR-2 with IC50 value of 0.31 ± 0.04 μM. Furthermore, a molecular docking of the tested compounds was carried out in order to investigate their binding pattern with the prospective target, VEGFR-2 (PDB-code: 4ASD).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt. Electronic address: wagdy2000@gmail.com.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fares
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
authors.forename: Hany S
authors.initials: HS
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, British University in Egypt, Cairo, Egypt; Department of Biology, The American University in Cairo, P.O. Box 11835, New Cairo, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Aly
authors.affiliation: Department of Biology, The American University in Cairo, P.O. Box 11835, New Cairo, Egypt.
authors.forename: Suher
authors.initials: S
authors.lastname: Zada
authors.affiliation: Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622 Giza, Egypt.
authors.forename: Mamdouh M
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, P.O. Box 11562, Egypt.
authors.forename: Sahar M
authors.initials: SM
authors.lastname: Abou-Seri
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt. Electronic address: hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abou El Ella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D014508:Urea; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Design; Docking; HepG2; Urea; VEGFR-2