Synthesis, characterization, preliminary SAR and molecular docking study of some novel substituted imidazo[2,1-lus-plus">b][1,3,4]thiadiazole derivatives as antifungal agents

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• 作者：Mustafa Er ; Buğracan Ergüven ; Hakan Tahtaci…
• 关键词：2 ; Amino ; [1 ; 3 ; 4]thiadiazole ; Imidazo[2 ; 1 ; b][1 ; 3 ; 4]thiadiazole ; Phenacyl bromide ; Molecular docking ; Antifungal activity ; SAR
• 刊名：Medicinal Chemistry Research
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：26
• 期：3
• 页码：615-630
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120
• 卷排序：26

文摘

The aim of this study was to synthesize imidazo[2,1-b][1,3,4]thiadiazole derivatives, characterize them with various spectroscopic methods and investigate their antifungal activities. 2-Αmino-1,3,4-thiadiazole derivatives 2a, b were synthesized by reacting nitrile compounds 1a, b with thiosemicarbazide (yields 75 and 88%). We then synthesized imidazo[2,1-b][1,3,4]thiadiazole derivatives 4–21, the target compounds, from the reactions of 2-amino-1,3,4-thiadiazole derivatives 2a, b with phenacyl bromide derivatives 3 (yields 52–69%). The structures of all synthesized compounds were characterized by infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, elemental analysis and mass spectroscopy and X-ray diffraction analysis was also used for the compounds 7, 8, 10, and 17. Subsequently, in vitro antifungal activity tests were applied to all synthesized compounds. Inhibition zones, percentages of inhibition and LD50 doses were determined. Most of the synthesized compounds exhibited good antifungal activity against plant pathogens. Molecular docking and electronic properties calculations were carried out in order to see the potential binding conformations of the ligands and the effect of the substituents on the activities. Docking score successfully reflects the activity of the most active compound 10, which was found to have the lowest octanol/water partition coefficient and high HOMO energy value. The combination of experimental and computational work show that all the synthesized compounds have promising activities and might serve as novel drug candidates.