title: Design, synthesis and evaluation of new marine alkaloid-derived pentacyclic structures with anti-tumoral potency.
abstract: This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1-11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA. s.boucle@hotmail.fr.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Boucle
authors.affiliation: University François Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales, 31 avenue Monge, 37200 Tours, France. celine.melin@univ-tours.fr.
authors.forename: Celine
authors.initials: C
authors.lastname: Melin
authors.affiliation: University François Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales, 31 avenue Monge, 37200 Tours, France. marc.clastre@univ-tours.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Clastre
authors.affiliation: University of Poitiers, UMR CNRS IC2MP 7285, 40 avenue du Recteur Pineau, 86022 Poitiers Cedex, France. jerome.guillard@univ-poitiers.fr.
authors.forename: Jerome
authors.initials: J
authors.lastname: Guillard
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015195:Drug Design; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry; D015363:Quinolones / Q000737:chemistry; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C428188:makaluvamine A