Lipase-catalyzed kinetic resolution of novel antifungal N-substituted benzimidazole derivatives

Edyta Łukowska-Chojnacka , Monika Staniszewska , Małgorzata Bondaryk , Jan Maurin , Maria Bretner

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).
Author Edyta Łukowska-Chojnacka (FC / IBC / DDTB)
Edyta Łukowska-Chojnacka,,
- Department Of Drug Technology And Biotechnology
, Monika Staniszewska - [National Institute of Public Health - National Institute of Hygiene (NIPH - NIH)]
Monika Staniszewska,,
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, Małgorzata Bondaryk - [National Institute of Public Health - National Institute of Hygiene (NIPH - NIH)]
Małgorzata Bondaryk,,
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, Jan Maurin - [National Center for Nuclear Research (NCBJ)]
Jan Maurin,,
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- Narodowe Centrum Badań Jądrowych w Otwocku
, Maria Bretner (FC / IBC / DDTB)
Maria Bretner,,
- Department Of Drug Technology And Biotechnology
Journal seriesChirality, ISSN 0899-0042
Issue year2016
Vol28
Pages347-354
Publication size in sheets0.5
Keywords in Englishazole; benzimidazole; enzyme; lipase; enzymatic transesterification; kinetic resolution; antifungal activity
ASJC Classification1605 Organic Chemistry; 1607 Spectroscopy; 3002 Drug Discovery; 3004 Pharmacology; 1503 Catalysis; 1602 Analytical Chemistry
DOIDOI:10.1002/chir.22591
URL http://onlinelibrary.wiley.com/doi/10.1002/chir.22591/full
Languageen angielski
File
wdpb_publikacje_pliki_plik_publikacja_2823_org.pdf 258.78 KB
Score (nominal)25
Score sourcejournalList
ScoreMinisterial score = 20.0, 12-07-2020, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 12-07-2020, ArticleFromJournal
Publication indicators WoS Citations = 4; Scopus Citations = 6; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.722; WoS Impact Factor: 2016 = 1.956 (2) - 2016=1.829 (5)
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