Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds ( - ) and evaluate their antifungal activity...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2017-11, Vol.22 (11), p.2004
Main Authors: Levent, Serkan, Kaya Çavuşoğlu, Betül, Sağlık, Begüm Nurpelin, Osmaniye, Derya, Acar Çevik, Ulviye, Atlı, Özlem, Özkay, Yusuf, Kaplancıklı, Zafer Asım
Format: Article
Language:English
Subjects:
1,3,4-oxadiazole
1,3,4-thiadiazole
Antifungal activity
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Biosynthesis
Candida
Candida - drug effects
Cytotoxicity
docking
Enzymes
Ergosterol
Fungi
Fungicides
Hybrids
Lanosterol
Microbial Sensitivity Tests
Minimum inhibitory concentration
Oxadiazoles
Oxadiazoles - chemistry
Oxadiazoles - pharmacology
Spectroscopy, Fourier Transform Infrared
Strong interactions (field theory)
Structure-Activity Relationship
Thiadiazoles
Thiadiazoles - chemistry
Thiadiazoles - pharmacology
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Summary:In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds ( - ) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, ¹H-NMR, C-NMR and HR-MS spectral data. Compounds were tested against four species by broth microdilution assay. Compounds , and , bearing a nitro group, showed significant antifungal activity against all fungi with minimum inhibitory concentration (MIC) in the range of 0.78-3.12 µg/mL. These compounds were also screened for their in vitro cytotoxic effects by MTT assay and detected as nontoxic at their active concentrations against strains. To examine the effects of these compounds on ergosterol biosynthesis, the LC-MS-MS method, which is based on quantification of ergosterol level in , was carried out. Finally, the most active molecule ( ) was docked in the active site of the lanosterol 14α-demethylase enzyme, and it was determined that there is a strong interaction between the compound and enzyme.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules22112004