Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton
| Autor: | Xiao-Ke Wang, Xiaoyan Han, Bao-Hua Chen, Yali Song, Yifan Zhong, Guan Zhou, Guo-chao Liang, Shengbin Li |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Antifungal Antifungal Agents Indoles medicine.drug_class Microbial Sensitivity Tests 010402 general chemistry 01 natural sciences Structure-Activity Relationship Candida albicans Drug Discovery medicine Structure–activity relationship Potency Chromans Indole test Cryptococcus neoformans Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Chemistry General Chemistry General Medicine biology.organism_classification In vitro 0104 chemical sciences Invasive fungal disease Biochemistry |
| Zdroj: | CHEMICAL & PHARMACEUTICAL BULLETIN. 64:1411-1416 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.c16-00366 |
| Popis: | Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents. |
| Databáze: | OpenAIRE |
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