title: Studies on quinones. Part 47. Synthesis of novel phenylaminophenanthridinequinones as potential antitumor agents.
abstract: In our search for potential anticancer agents, a series of 8- and 9-phenylamino-3,4-tetrahydro-phenanthridine-1,7,10(2H)-triones with substituent variations at 6-, 8- and 9-positions were prepared using a highly efficient sequence involving: a) solar photoacylation reactions of benzoquinone with arylaldehydes, b) one-pot procedure for the synthesis of 3,4-dihydrophenanthridine-1,7,10(2H)-trione intermediates from acylhydroquinones and c) highly regiocontrolled acid-induced amination reaction of phenanthridinequinones with phenylamines. The members of this series were in vitro evaluated using the MTT colorimetric method against one normal cell line and three human cancer cell lines. The SAR analysis indicates that the location of nitrogen substituents on the quinone nucleus, the presence of methyl, phenyl, furyl and thienyl groups at the 6-position and the aromatization of the angular cycloaliphatic ring of the phenylamino-3,4-tetrahydrophenanthridine-1,7,10(2H)-trione pharmacophore play key roles in the antitumor activity.
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile. jvalderr@uc.cl
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Valderrama
authors.forename: Andrea
authors.initials: A
authors.lastname: Ibacache
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: Cristina
authors.initials: C
authors.lastname: Theoduloz
authors.forename: Julio
authors.initials: J
authors.lastname: Benites
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D015394:Molecular Structure; D010617:Phenanthridines / Q000737:chemistry*; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D010617:Phenanthridines; D011809:Quinones