Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains

In order to explore novel antifungal agents, twenty-seven triazole derivatives featuring an alkyne linker in the side chain were designed and synthesized by the Sonogashira reaction. Most of the target compounds exhibited good antifungal activity against eight human pathogenic fungi, especially exce...

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Main Authors:	Tingjunhong Ni, Lei Pang, Zhan Cai, Fei Xie, Zichao Ding, Yumeng Hao, Ran Li, Shichong Yu, Xiaoyun Chai, Ting Wang, Yongsheng Jin, Dazhi Zhang, Yuanying Jiang
Format:	Article
Language:	English
Published:	Elsevier 2019-07-01
Series:	Journal of Saudi Chemical Society
Online Access:	http://www.sciencedirect.com/science/article/pii/S1319610318301133

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spelling	doaj-41f087e2073f46209585d7a12b900e6d2020-11-24T21:48:59ZengElsevierJournal of Saudi Chemical Society1319-61032019-07-01235576585Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chainsTingjunhong Ni0Lei Pang1Zhan Cai2Fei Xie3Zichao Ding4Yumeng Hao5Ran Li6Shichong Yu7Xiaoyun Chai8Ting Wang9Yongsheng Jin10Dazhi Zhang11Yuanying Jiang12Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, ChinaDepartment of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China; Corresponding authors.Department of Pharmacology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China; Corresponding authors.In order to explore novel antifungal agents, twenty-seven triazole derivatives featuring an alkyne linker in the side chain were designed and synthesized by the Sonogashira reaction. Most of the target compounds exhibited good antifungal activity against eight human pathogenic fungi, especially excellent activity against Candida and Cryptococcus species, comparing with the reference drugs fluconazole, voriconazole and ravuconazole. Compounds A2 and A3 exhibited in vitro activity against all the tested fungi with MIC80 values ranging from 0.0156 μg/mL to 0.5 μg/mL, which are superior to ravuconazole and fluconazole. SAR and molecular docking study give a clear conclusion that para-fluoro, para-chloro, and para-cyano substituted phenylalkynyl or pyridinylalkynyl side chains may promote triazole antifungal activity. Keywords: Triazole, Alkyne, CYP51, Antifungal, Synthesishttp://www.sciencedirect.com/science/article/pii/S1319610318301133
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Tingjunhong Ni Lei Pang Zhan Cai Fei Xie Zichao Ding Yumeng Hao Ran Li Shichong Yu Xiaoyun Chai Ting Wang Yongsheng Jin Dazhi Zhang Yuanying Jiang
spellingShingle	Tingjunhong Ni Lei Pang Zhan Cai Fei Xie Zichao Ding Yumeng Hao Ran Li Shichong Yu Xiaoyun Chai Ting Wang Yongsheng Jin Dazhi Zhang Yuanying Jiang Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains Journal of Saudi Chemical Society
author_facet	Tingjunhong Ni Lei Pang Zhan Cai Fei Xie Zichao Ding Yumeng Hao Ran Li Shichong Yu Xiaoyun Chai Ting Wang Yongsheng Jin Dazhi Zhang Yuanying Jiang
author_sort	Tingjunhong Ni
title	Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
title_short	Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
title_full	Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
title_fullStr	Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
title_full_unstemmed	Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
title_sort	design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains
publisher	Elsevier
series	Journal of Saudi Chemical Society
issn	1319-6103
publishDate	2019-07-01
description	In order to explore novel antifungal agents, twenty-seven triazole derivatives featuring an alkyne linker in the side chain were designed and synthesized by the Sonogashira reaction. Most of the target compounds exhibited good antifungal activity against eight human pathogenic fungi, especially excellent activity against Candida and Cryptococcus species, comparing with the reference drugs fluconazole, voriconazole and ravuconazole. Compounds A2 and A3 exhibited in vitro activity against all the tested fungi with MIC80 values ranging from 0.0156 μg/mL to 0.5 μg/mL, which are superior to ravuconazole and fluconazole. SAR and molecular docking study give a clear conclusion that para-fluoro, para-chloro, and para-cyano substituted phenylalkynyl or pyridinylalkynyl side chains may promote triazole antifungal activity. Keywords: Triazole, Alkyne, CYP51, Antifungal, Synthesis
url	http://www.sciencedirect.com/science/article/pii/S1319610318301133
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Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains

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