title: Lipase-Catalyzed Kinetic Resolution of Novel Antifungal N-Substituted Benzimidazole Derivatives.
abstract: A series of new N-substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase-catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100).
authors.affiliation: Faculty of Chemistry, Institute of Biotechnology, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Łukowska-Chojnacka
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Staniszewska
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bondaryk
authors.affiliation: National Centre for Nuclear Research, Otwock, Poland.|National Medicines Institute, Warsaw, Poland.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Maurin
authors.affiliation: Faculty of Chemistry, Institute of Biotechnology, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bretner
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D002384:Catalysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001562:Benzimidazoles; D008049:Lipase
keywords: antifungal activity; azole; benzimidazole; enzymatic transesterification; enzyme; kinetic resolution; lipase