title: Synthesis and cytotoxic activity of psorospermin and acronycine analogues in the 3-propyloxy-acridin-9(10H)-one and -benzo[b]acridin-125H-one series.
abstract: In order to explore the structure-activity relationships in the acronycine and psorospermin series, simplified analogues of the highly cytotoxic (+/-)-(2R*,1'R*)-5-methoxy-11-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-11H-furo[2,3-c]acridin-6-one and (+/-)-(2R*,1'R*)-5-methoxy-13-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-13H-benzo[b]furo[3,2-h]-acridin-6-one lacking the fused furan ring, including 3-allyloxy-1-methoxy-10-methyl-acridin-9(10H)-one, 3-allyloxy-1-methoxy-5-methyl-benzo[b]acridin-12(5H)-one, the corresponding epoxides, and related dihydrodiol esters and diesters were prepared. Only the simplified oxirane compounds displayed significant antiproliferative activity compared to the parent compounds. The oxirane alkylating unit appears indispensible to observe significant antiproliferative activity in both series, but the presence of the angularly fused furan ring does not appear as a crucial structural requirement to observe significant cytotoxic activity.
authors.affiliation: Laboratoire de Pharmacognosie de l'Université Paris Descartes, UMR/CNRS n degrees 8638, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boutefnouchet
authors.forename: Nguyen Tuan
authors.initials: NT
authors.lastname: Minh
authors.forename: Rana
authors.initials: R
authors.lastname: Putrus
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Alain
authors.initials: A
authors.lastname: Pierré
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Lallemand
mesh_terms: D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones; C025543:psorospermin; D000175:Acronine