Format

Send to

Choose Destination
Int J Mol Sci. 2017 Jan 17;18(1). pii: E177. doi: 10.3390/ijms18010177.

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

Author information

1
Department of Pharmaceutical Chemistry, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania. teodora_anca@yahoo.com.
2
Department of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 3-5 Manăştur Street, RO-400372 Cluj-Napoca, Romania. dan.vodnar@usamvcluj.ro.
3
National Institute for Research and Development for Cryogenic and Isotopic Technologies, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania. radu.tamaian@icsi.ro.
4
SC Biotech Corp SRL, 4th Uzinei Street, RO-240050 Râmnicu Vâlcea, Romania. radu.tamaian@icsi.ro.
5
National Institute for Research and Development of Isotopic and Molecular Technologies, RO-400293 Cluj-Napoca, Romania. adrian.pirnau@itim-cj.ro.
6
Department of Pharmaceutical Technology and Biopharmaceutics, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania. vlaselaur@yahoo.com.
7
Department of Pharmaceutical Chemistry, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania. ionut.ioana@umfcluj.ro.
8
Department of Pharmaceutical Chemistry, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania. onigao65@yahoo.com.
9
Department of Pharmaceutical Chemistry, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania. brandu32@yahoo.com.

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.

KEYWORDS:

ADME-Tox predictors; antifungal activity; lanosterol 14α-demethylase; lipophilicity; molecular docking; thiazolin-4-one

PMID:
28106743
PMCID:
PMC5297809
DOI:
10.3390/ijms18010177
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center