title: Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives.
abstract: 1-Methyl-2-phenyl (1) and 1,3-dimethyl-2-phenyl (2)-substituted pyrrole[2,3-d]pyridazinones, as well as their tetracyclic analogues 3-6, were synthesized and evaluated in vitro by the National Cancer Institute against 60 human tumor cell lines derived from nine cancer cell types. Biological results showed that the antitumor activities of these compounds were related to the planarity of their ring systems with potency increasing in the order 2<4 congruent with 5<6<3. Among them, the most potent compound 3 showed significant cell line cytotoxicity, particularly against the renal cancer subpanel [GI(50) (microM) 5.07] and displayed significant potency [GI(50) (microM) 3.04-4.32] against MOLT-4, SR (leukemia), NCI-H460 (non-small cell lung), HCT-116 (colon), and SF-295 (CNS) cancer cells, respectively.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cignarella
authors.forename: Giorgio
authors.initials: G
authors.lastname: Chelucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Loriga
authors.forename: Gérard Aimè
authors.initials: GA
authors.lastname: Pinna
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011724:Pyridazines; C464599:pyrrole(2,3-d)pyridazin-4-one