Synthesis of novel tetrazole derivatives and evaluation of their antifungal activity

Edyta Łukowska-Chojnacka , Jolanta Mierzejewska , Małgorzata Milner-Krawczyk , Monika Staniszewska , Małgorzata Bondaryk

Abstract

With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfanyl]-1,3-benzoxazole and Michael-type addition of aryltetrazole to phenyl vinyl sulfone. The chemical structures of the synthesized compounds were confirmed by means of 1H NMR, 13C NMR, IR and HRMS spectral data. The compounds were tested against the moulds: Fusarium sambucinum, Fusarium oxysporum, Colletotrichum coccodes, Aspergillus niger, and the yeast Candida albicans. The results showed that among the moulds only C. coccodes was significantly sensitive to all the structures examined. All the tetrazole derivatives acted at the same level against C. albicans and demonstrated a high cell growth inhibition (97–99%) at the concentrations ranging from 16 to 0.0313 lg/mL. The mode of action of 2-({3-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5c) and 2-({3-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5d) was established by verifying fungal growth in the presence of osmotic protector-sorbitol. The effect of compound 5c or 5d combined with Fluconazole was determined using the checkerboard method. The calculated fractional inhibitory concentration index (FIC) indicated antagonism (FIC >1). Additionally, survival experiments with lepidopteran Galleria mellonella treated with compounds 5c and 5d were performed and demonstrated the lack of toxicity of these compounds.
Author Edyta Łukowska-Chojnacka ZTiBSL
Edyta Łukowska-Chojnacka,,
- Department Of Drug Technology And Biotechnology
, Jolanta Mierzejewska ZTiBSL
Jolanta Mierzejewska,,
- Department Of Drug Technology And Biotechnology
, Małgorzata Milner-Krawczyk ZTiBSL
Małgorzata Milner-Krawczyk,,
- Department Of Drug Technology And Biotechnology
, Monika Staniszewska
Monika Staniszewska,,
-
, Małgorzata Bondaryk
Małgorzata Bondaryk,,
-
Journal seriesBioorganic & Medicinal Chemistry, ISSN 0968-0896
Issue year2016
Vol24
No22
Pages6058-6065
Publication size in sheets0.5
Keywords in Englishtetrazole, benzothiazole, benzoxazole, azole, antifungal activity
DOIDOI:10.1016/j.bmc.2016.09.066
URL http://dx.doi.org/10.1016/j.bmc.2016.09.066
Languageen angielski
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Score (nominal)30
ScoreMinisterial score = 25.0, 28-11-2017, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 28-11-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.93 (2) - 2016=2.88 (5)
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