title: Antifungal activity of some mono, bis and quaternary Mannich bases derived from acetophenone.
abstract: The development of resistance to current antifungal therapeutics drives search for new effective agents. Some Mannich bases have antifungal activity, but no information is available regarding the antifungal activity of acetophenone derived Mannich bases. Mono Mannich bases of acetophenone 1-3 were synthesized and converted into their corresponding bis derivatives, 5-7. Representative quaternary derivatives 4 and 8 were also synthesized. Antifungal activities of the compounds were evaluated using some yeasts and dermatophytes in vitro. Mono Mannich base 3 and quaternary compounds 4 and 8 were found to be 2-16 times more potent than the reference compound amphotericin B against dermatophytes: Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum canis. Compounds 4 and 8 were also found to be 2 times more effective compared with amphotericin B against the yeast Saccharomyces cerevisiae. Quaternization procedure improved the biological activity dramatically, whereas conversion of mono Mannich bases to corresponding bis derivatives generally did not affect antifungal activity. Our results suggest that acetophenone derived mono Mannich base 3 and quaternary derivatives 4 and 8 may serve as leading compounds for further studies to develop new antifungal agents with their highly potent antifungal activity.
authors.affiliation: Department of Chemistry, University of Kuopio, Kuopio, Finland. incigul@mailcity.com
authors.forename: H I
authors.initials: HI
authors.lastname: Gul
authors.forename: T
authors.initials: T
authors.lastname: Ojanen
authors.forename: J
authors.initials: J
authors.lastname: Vepsalainen
authors.forename: M
authors.initials: M
authors.lastname: Gul
authors.forename: E
authors.initials: E
authors.lastname: Erciyas
authors.forename: O
authors.initials: O
authors.lastname: Hanninen
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000187:drug effects
chemical_list: D000098:Acetophenones; D000935:Antifungal Agents; D008352:Mannich Bases