Karaca Gençer Hülya, Acar Çevik Ulviye, Levent Serkan, Sağlık Begüm Nurpelin, Korkut Büşra, Özkay Yusuf, Ilgın Sinem, Öztürk Yusuf
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Molecules. 2017 Mar 27;22(4):507. doi: 10.3390/molecules22040507.
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1-benzimidazol-2-yl)phenyl)-4-substituted-4-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds , , , , , , and possess a good antifungal profile. Compounds was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds , , , , , and showed that compounds and 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 . Compounds and inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound against at cellular level. It was determined that compound has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.
由于对抗真菌剂的需求不断增长，我们合成了一系列新的2-((5-(4-(5-取代-1-苯并咪唑-2-基)苯基)-4-取代-4-1,2,4-三唑-3-基)硫代)-1-(取代苯基)乙-1-酮衍生物，并对其进行了抗真菌测试。通过傅里叶变换红外光谱(FT-IR)、¹H-核磁共振(¹H-NMR)、碳-核磁共振(C-NMR)和高分辨率质谱(HR-MS)对合成的化合物进行了表征和结构解析。采用肉汤微量稀释法对合成的化合物进行了体外抗念珠菌活性筛选。通过MTT法测定了最终化合物的体外细胞毒性作用。微生物学研究表明，化合物、、、、、和具有良好的抗真菌活性。化合物是活性最高的衍生物，其抗真菌活性与参考药物酮康唑和氟康唑相当。对化合物、、、、、和的细胞毒性评估表明，化合物和是细胞毒性最小的药物。通过基于测定中麦角甾醇水平的液相色谱-串联质谱(LC-MS-MS)法观察了这两种化合物对麦角甾醇生物合成的影响。化合物和浓度依赖性地抑制麦角甾醇生物合成。进行了荧光显微镜研究，以在细胞水平上观察化合物对的作用。确定化合物具有膜损伤作用，这可能与抑制麦角甾醇生物合成有关。
