title: Synthesis of N-(5,7-diamino-3-phenyl-quinoxalin-2-yl)-3,4,5-substituted anilines and N-[4[(5,7-diamino-3-phenylquinoxalin-2-yl)amino]benzoyl]-l-glutamic acid diethyl ester: evaluation of in vitro anti-cancer and anti-folate activities.
abstract: Several diamino quinoxalines were designed, synthesized and evaluated as anti-tumor agents. Two compounds showed the most potent cytotoxic activities against the leukemia CCRF-CEM cell line (GI(50)<0.01microM) and the ovarian cancer cell line OVCAR-4 (GI(50)=0.03microM), respectively, with comparable/better activities than Methotrexate (MTX). Docking calculations of the complexes of hDHFR with the most active compounds identified the binding mode of the described molecules with respect to MTX.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy. pcorona@uniss.it
authors.forename: Paola
authors.initials: P
authors.lastname: Corona
authors.forename: Mario
authors.initials: M
authors.lastname: Loriga
authors.forename: M Paola
authors.initials: MP
authors.lastname: Costi
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglietti
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005971:Glutamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011810:Quinoxalines / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005971:Glutamates; D011810:Quinoxalines; C011829:glutamic acid diethyl ester; C023650:aniline