title: Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents.
abstract: A series of novel 3-substituted amino-4-hydroxycoumarin derivatives have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their CHS inhibition activity and antimicrobial activity in vitro. The enzymatic assay indicated that most of the compounds have good inhibitory activity against CHS, in which compound 6o with IC50 of 0.10 mmol/L had stronger activity than that of polyoxins B, which acts as control drug with IC50 of 0.18 mmol/L. As far as the antifungal activity is concerned, most of the compounds possessed moderate to excellent activity against some representative pathogenic fungi. Especially, compound 6b was found to be the most potent agent against Cryptococcus neoformans with minimal inhibitory concentration (MIC) of 4 μg/mL. Moreover, the results of antibacterial screening showed that these compounds have negligible actions to some tested bacteria. Therefore, these compounds would be promising to develop selective antifungal agents.
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Zhiqiang
authors: Z
authors: Ge
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Qinggang
authors: Q
authors: Ji
authors: b Unit for Analytical Probe and Protein Biotechnology, Key Laboratory of Clinical Laboratory Diagnostics of the Education Ministry , College of Laboratory Medicine, Chongqing Medical University , Chongqing , PR China.
authors: Chunyan
authors: C
authors: Chen
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Qin
authors: Q
authors: Liao
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Hualong
authors: H
authors: Wu
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Xiaofei
authors: X
authors: Liu
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Yanrong
authors: Y
authors: Huang
authors: a Key Laboratory of Applied Chemistry of Chongqing Municipality , School of Chemistry and Chemical Engineering, Southwest University , Chongqing , PR China and.
authors: Lvjiang
authors: L
authors: Yuan
authors: b Unit for Analytical Probe and Protein Biotechnology, Key Laboratory of Clinical Laboratory Diagnostics of the Education Ministry , College of Laboratory Medicine, Chongqing Medical University , Chongqing , PR China.
authors: Fei
authors: F
authors: Liao
mesh_terms: D015110:4-Hydroxycoumarins / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D003455:Cryptococcus neoformans / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D015110:4-Hydroxycoumarins; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D002687:Chitin Synthase; C068805:4-hydroxycoumarin
keywords: 3-substituted amino-4-hydroxycoumarin; Antifungal agent; chitin synthase; chitin synthase inhibitor