title: Canthin-4-ones as Novel Antibacterial Agents.
abstract: Based on the chemotype of canthin-4-one alkaloids with moderate antimicrobial activity, a collection of variously substituted canthin-4-ones and desaza analogs were synthesized. Key steps in the syntheses were regioselective halogenations of (desaza) canthin-4-one, followed by Pd-catalyzed cross-coupling reactions. The in vitro screening for antimicrobial activity revealed that two 5-substituted canthin-4-ones (3-pyridyl, 2-bromophenyl) exhibit significant activity against Streptococcus entericus, coupled with high selectivity and the lack of cytotoxicity against mammalian cells. The intact canthin-4-one ring system was demonstrated to be essential for antibacterial activity.
authors: Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Tim
authors: T
authors: Tremmel
authors: Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Andreas
authors: A
authors: Puzik
authors: Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: André P
authors: AP
authors: Gehring
authors: Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-University of Munich, Munich, Germany. franz.bracher@cup.uni-muenchen.de.
authors: Franz
authors: F
authors: Bracher
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002243:Carbolines; D026121:Indole Alkaloids; C000614893:canthin-4-one
keywords: Alkaloids; Antibacterial activity; Canthin-4-ones; Streptococcus