title: Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton.
abstract: 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.
authors.affiliation: Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Han
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Zhong
authors.forename: Sheng-Bin
authors.initials: SB
authors.lastname: Li
authors.forename: Guo-Chao
authors.initials: GC
authors.lastname: Liang
authors.forename: Guan
authors.initials: G
authors.lastname: Zhou
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Wang
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Chen
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Song
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D002839:Chromans; D007211:Indoles