Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

PANG Lei; ZHAO Jing; NI Tingjunhong; ZANG Chengxu; DING Zichao; ZHANG Dazhi; JIANG Yuanying

doi:10.3969/j.issn.1006-0111.2017.01.005

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Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties, novel compounds bearing both quinoline and thiophene were designed, synthesized, and evaluated for in vitro antifungal activity against Candida albicans. Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-carbaldehyde as starting materials, 13 compounds were synthesized via reductive amination, reduction of cyano group and amidation of quinoline-or isoquinoline-carboxylic acid. Their chemical structures were characterized by ¹H NMR and MS. In vitro antifungal screening against Candida albicans SC5314 was performed with the microbroth dilution method. Results All the compounds exhibited potent antifungal activities against Candida albicans. Among them, compound 6k showed the highest antifungal activity with MIC₈₀ value of 0.5 μg/ml, which is same potent as fluconazole. Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities, and deserve further research.

Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350112, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-10-08

Rev Recd Date: 2016-11-29

Key words:

Abstract: Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties, novel compounds bearing both quinoline and thiophene were designed, synthesized, and evaluated for in vitro antifungal activity against Candida albicans. Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-carbaldehyde as starting materials, 13 compounds were synthesized via reductive amination, reduction of cyano group and amidation of quinoline-or isoquinoline-carboxylic acid. Their chemical structures were characterized by ¹H NMR and MS. In vitro antifungal screening against Candida albicans SC5314 was performed with the microbroth dilution method. Results All the compounds exhibited potent antifungal activities against Candida albicans. Among them, compound 6k showed the highest antifungal activity with MIC₈₀ value of 0.5 μg/ml, which is same potent as fluconazole. Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities, and deserve further research.

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Reference (19)

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Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

doi: 10.3969/j.issn.1006-0111.2017.01.005

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