Murineddu, Gabriele and Cignarella, Giorgio and Chelucci, Giorgio Adolfo and Loriga, Giovanni and Pinna, Gérard Aimé (2002) Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives. Chemical and Pharmaceutical Bulletin, Vol. 50 (6), p. 754-759. eISSN 1347-5223. Article.
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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 5<6<3. Among them, the most potent compound 3 showed significant cell line cytotoxicity, particularly against the renal cancer subpanel [GI50 (µM) 5.07] and displayed significant potency [GI50 (µM) 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.
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