Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives.
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.
Murineddu
Gabriele
G
Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Italy.
Cignarella
Giorgio
G
Chelucci
Giorgio
G
Loriga
Giovanni
G
Pinna
Gérard Aimè
GA
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
D000970:Antineoplastic Agents; D011724:Pyridazines; C464599:pyrrole(2,3-d)pyridazin-4-one