title: Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity.
abstract: Certain pyridazine containing compounds 2a-f, 3a, b, 4a, b, 5a, b, 6a and b were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were screened for their cytotoxic activity in vitro on colon cancer cell line (HCT-116) and breast cancer cell line (MCF-7). In addition, the antitumor activity of the synthesized compounds was tested in vivo against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. The in vitro vascular endothelial growth factor receptor (VEGFR) enzyme inhibition assay was carried out for the most active compounds at a single dose of 10 µM. The obtained results revealed that compound 5b, which showed potent cytotoxic activity against HCT-116 also, exhibited the highest inhibition in the VEGFR kinase assay (92.2%).
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University.
authors.forename: Salwa
authors.initials: S
authors.lastname: Elmeligie
authors.forename: Eman Mohamed
authors.initials: EM
authors.lastname: Ahmed
authors.forename: Suzan Mohamed
authors.initials: SM
authors.lastname: Abuel-Maaty
authors.forename: Sawsan Abo-Bakr
authors.initials: SA
authors.lastname: Zaitone
authors.forename: Demiana Samir
authors.initials: DS
authors.lastname: Mikhail
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C062482:pyridazine; D040262:Receptors, Vascular Endothelial Growth Factor