New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characte...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/4/507 |
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| author | Hülya Karaca Gençer Ulviye Acar Çevik Serkan Levent Begüm Nurpelin Sağlık Büşra Korkut Yusuf Özkay Sinem Ilgın Yusuf Öztürk |
| author_facet | Hülya Karaca Gençer Ulviye Acar Çevik Serkan Levent Begüm Nurpelin Sağlık Büşra Korkut Yusuf Özkay Sinem Ilgın Yusuf Öztürk |
| author_sort | Hülya Karaca Gençer |
| collection | DOAJ |
| description | Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5t, 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol. |
| first_indexed | 2024-12-10T08:52:30Z |
| format | Article |
| id | doaj.art-14f1a80d4f4b4c959703311ea2d8ac56 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T08:52:30Z |
| publishDate | 2017-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-14f1a80d4f4b4c959703311ea2d8ac562022-12-22T01:55:33ZengMDPI AGMolecules1420-30492017-03-0122450710.3390/molecules22040507molecules22040507New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity EvaluationHülya Karaca Gençer0Ulviye Acar Çevik1Serkan Levent2Begüm Nurpelin Sağlık3Büşra Korkut4Yusuf Özkay5Sinem Ilgın6Yusuf Öztürk7Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDoping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyOwing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5t, 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.http://www.mdpi.com/1420-3049/22/4/5071,2,4-triazoleantifungal activityergosterolcytotoxicityNIH/3T3 |
| spellingShingle | Hülya Karaca Gençer Ulviye Acar Çevik Serkan Levent Begüm Nurpelin Sağlık Büşra Korkut Yusuf Özkay Sinem Ilgın Yusuf Öztürk New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation Molecules 1,2,4-triazole antifungal activity ergosterol cytotoxicity NIH/3T3 |
| title | New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation |
| title_full | New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation |
| title_fullStr | New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation |
| title_full_unstemmed | New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation |
| title_short | New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation |
| title_sort | new benzimidazole 1 2 4 triazole hybrid compounds synthesis anticandidal activity and cytotoxicity evaluation |
| topic | 1,2,4-triazole antifungal activity ergosterol cytotoxicity NIH/3T3 |
| url | http://www.mdpi.com/1420-3049/22/4/507 |
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