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Int. J. Mol. Sci. 2017, 18(1), 177; doi:10.3390/ijms18010177

Design, Synthesis and Antifungal Activity Evaluation of New Thiazolin-4-ones as Potential Lanosterol 14α-Demethylase Inhibitors

1
Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania
2
Department of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 3-5 Manăştur Street, RO-400372 Cluj-Napoca, Romania
3
National Institute for Research and Development for Cryogenic and Isotopic Technologies, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania
4
SC Biotech Corp SRL, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania
5
National Institute for Research and Development of Isotopic and Molecular Technologies, RO-400293 Cluj-Napoca, Romania
6
Department of Pharmaceutical Technology and Biopharmaceutics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania
*
Authors to whom correspondence should be addressed.
Academic Editor: Christo Christov
Received: 22 November 2016 / Revised: 6 January 2017 / Accepted: 9 January 2017 / Published: 17 January 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3502 KB, uploaded 19 January 2017]   |  

Abstract

Twenty-three thiazolin-4-ones were synthesized starting from phenylthioamide or thiourea derivatives by condensation with α-monochloroacetic acid or ethyl α-bromoacetate, followed by substitution in position 5 with various arylidene moieties. All the synthesized compounds were physico-chemically characterized and the IR (infrared spectra), 1H NMR (proton nuclear magnetic resonance), 13C NMR (carbon nuclear magnetic resonance) and MS (mass spectrometry) data were consistent with the assigned structures. The synthesized thiazolin-4-one derivatives were tested for antifungal properties against several strains of Candida and all compounds exhibited efficient anti-Candida activity, two of them (9b and 10) being over 500-fold more active than fluconazole. Furthermore, the compounds’ lipophilicity was assessed and the compounds were subjected to in silico screening for prediction of their ADME-Tox properties (absorbtion, distribution, metabolism, excretion and toxicity). Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. The results of the in vitro antifungal activity screening, docking study and ADME-Tox prediction revealed that the synthesized compounds are potential anti-Candida agents that might act by inhibiting the fungal lanosterol 14α-demethylase and can be further optimized and developed as lead compounds. View Full-Text
Keywords: thiazolin-4-one; antifungal activity; lipophilicity; lanosterol 14α-demethylase; molecular docking; ADME-Tox predictors thiazolin-4-one; antifungal activity; lipophilicity; lanosterol 14α-demethylase; molecular docking; ADME-Tox predictors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Stana, A.; Vodnar, D.C.; Tamaian, R.; Pîrnău, A.; Vlase, L.; Ionuț, I.; Oniga, O.; Tiperciuc, B. Design, Synthesis and Antifungal Activity Evaluation of New Thiazolin-4-ones as Potential Lanosterol 14α-Demethylase Inhibitors. Int. J. Mol. Sci. 2017, 18, 177.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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