title: Synthesis and antitumor activity of new derivatives of xanthen-9-one-4-acetic acid.
abstract: Xanthen-9-one-4-acetic acid (XAA) analogues in which the substituents in positions 5 and 6 are included in cyclic structures are described. Direct in vitro toxicity of the synthesized compounds against four tumor cell lines was evaluated, and their ability to stimulate mouse peritoneal macrophages and human monocytes in culture to become tumoricidal (indirect toxicity) was also studied. Despite low direct toxicity, almost all the compounds proved to be able to significantly enhance the lytic properties of both murine macrophages and human monocytes as well as the parent compound XAA and its most active derivative DMXAA taken as reference. In particular, compounds 4a, 5a, 7a, 13a,b, and 16a,b showed higher activity than the lead compound on human monocytes, compound 7a being 2.5 times more active than DMXAA, which is the most potent compound synthesized so far. Moreover, compounds 4a, 5a, 7a, 13a, 16a, and 16b proved to be able to induce TNF production in human immune cells.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Piero
authors.initials: P
authors.lastname: Valenti
authors.forename: Anna
authors.initials: A
authors.lastname: Caputo
authors.forename: Antonella
authors.initials: A
authors.lastname: Zampiron
authors.forename: Maria
authors.initials: M
authors.lastname: Carrara
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014966:Xanthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes