title: Novel Sulfonamide Derivatives Carrying a Biologically Active 3,4-Dimethoxyphenyl Moiety as VEGFR-2 Inhibitors.
abstract: Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR,1H-NMR,13C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Saud University.
authors.forename: Mostafa Mohammed
authors.initials: MM
authors.lastname: Ghorab
authors.forename: Mansour Sulaiman
authors.initials: MS
authors.lastname: Alsaid
authors.forename: Yassin Mohammed
authors.initials: YM
authors.lastname: Nissan
authors.forename: Abdelkader Elbadawy
authors.initials: AE
authors.lastname: Ashour
authors.forename: Abdullah Abdulalrahman
authors.initials: AA
authors.lastname: Al-Mishari
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmed
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D000069439:Dasatinib