title: Amino- and glycoconjugates of pyrido[4,3,2-kl]acridine. Synthesis, antitumor activity, and DNA binding.
abstract: A series of amino- and glycoconjugates of pyrido[4,3,2-kl]acridine and pyrido[4,3,2-kl]acridin-4-one have been prepared. The most active molecules, the amino conjugates 7 and 11, display a cytostatic activity against HT-29 cancer cells at micromolar concentration. This activity correlates well with a strong DNA binding. The molecules, amino or glycoconjugates, bind DNA by intercalation, the amino or glyco substituent being located in one groove. None of the molecules inhibits topoisomerase activity.
authors.affiliation: LEDSS UMR5616 & ICMG-FR2607, Université Joseph Fourier, BP53, 38041 Grenoble cedex 9, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bouffier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Baldeyrou
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Hildebrand
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
authors.forename: Danièle
authors.initials: D
authors.lastname: Carrez
authors.forename: Alain
authors.initials: A
authors.lastname: Croisy
authors.forename: Olivier
authors.initials: O
authors.lastname: Renaudet
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Martine
authors.initials: M
authors.lastname: Demeunynck
mesh_terms: D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000586:Amination; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018983:DNA Footprinting; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D006031:Glycosylation; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D044366:Transition Temperature
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D011725:Pyridines; D004247:DNA; D003850:Deoxyribonuclease I; D004264:DNA Topoisomerases, Type I