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 (6a–6s) and evaluate their antifungal activi...
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doaj-6a8b44c1acf14c09affcafaec38621ca2020-11-24T21:18:32ZengMDPI AGMolecules1420-30492017-11-012211200410.3390/molecules22112004molecules22112004Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal ActivitySerkan Levent0Betül Kaya Çavuşoğlu1Begüm Nurpelin Sağlık2Derya Osmaniye3Ulviye Acar Çevik4Özlem Atlı5Yusuf Özkay6Zafer Asım Kaplancıklı7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, TurkeyIn 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 (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, 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 Candida 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 C. krusei, was carried out. Finally, the most active molecule (6e) 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.https://www.mdpi.com/1420-3049/22/11/20041,3,4-oxadiazole1,3,4-thiadiazoleantifungal activityergosterolcytotoxicitydocking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Serkan Levent Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Ulviye Acar Çevik Özlem Atlı Yusuf Özkay Zafer Asım Kaplancıklı |
spellingShingle |
Serkan Levent Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Ulviye Acar Çevik Özlem Atlı Yusuf Özkay Zafer Asım Kaplancıklı Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity Molecules 1,3,4-oxadiazole 1,3,4-thiadiazole antifungal activity ergosterol cytotoxicity docking |
author_facet |
Serkan Levent Betül Kaya Çavuşoğlu Begüm Nurpelin Sağlık Derya Osmaniye Ulviye Acar Çevik Özlem Atlı Yusuf Özkay Zafer Asım Kaplancıklı |
author_sort |
Serkan Levent |
title |
Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity |
title_short |
Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity |
title_full |
Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity |
title_fullStr |
Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity |
title_full_unstemmed |
Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity |
title_sort |
synthesis of oxadiazole-thiadiazole hybrids and their anticandidal activity |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-11-01 |
description |
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 (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, 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 Candida 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 C. krusei, was carried out. Finally, the most active molecule (6e) 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. |
topic |
1,3,4-oxadiazole 1,3,4-thiadiazole antifungal activity ergosterol cytotoxicity docking |
url |
https://www.mdpi.com/1420-3049/22/11/2004 |
work_keys_str_mv |
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