title: Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.
abstract: The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.
authors.affiliation: Laboratoire HIT, case 552, (iSm2-UMR 6263)-Université Paul Cézanne, Faculté St Jérôme, 13397 Marseille, Cedex 20, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Benchabane
authors.forename: Carole
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Gérard
authors.initials: G
authors.lastname: Boyer
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Sabatier
authors.forename: Diane
authors.initials: D
authors.lastname: Allegro
authors.forename: Vincent
authors.initials: V
authors.lastname: Peyrot
authors.forename: Michel
authors.initials: M
authors.lastname: De Méo
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D000215:Acylation; D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008027:Light; D015162:Micronucleus Tests; D015394:Molecular Structure; D010777:Photochemistry; D011370:Proflavine / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D011370:Proflavine