Design, Synthesis, Antifungal Activity and Molecular Docking of Thiochroman-4-one Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 65; no. 10; pp. 904 - 910
• Main Authors: Zhong, Yifan, Han, Xiaoyan, Li, Shengbin, Qi, Hui, Song, Yali, Qiao, Xiaoqiang
• Format: Journal Article
• Language: English; Japanese
• Published: TOKYO The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: Acyltransferases - chemistry; Acyltransferases - metabolism; antifungal; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Binding Sites; Candida albicans - drug effects; Catalytic Domain; Chemical synthesis; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Chromans - chemical synthesis; Chromans - chemistry; Chromans - pharmacology; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Derivatives; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Fluconazole; Fluconazole - pharmacology; Fungi; Fungicides; inhibitor; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Minimum inhibitory concentration; Molecular docking; Molecular Docking Simulation; N-Myristoyltransferase; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; thiochroman-4-one; antifungal; ALBICANS N-MYRISTOYLTRANSFERASE; INFECTIONS; POTENT; molecular docking; inhibitor; thiochroman-4-one; SELECTIVE INHIBITORS; EPIDEMIOLOGY; DISCOVERY; N-myristoyltransferase
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c17-00274

N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for treatment of fungal infections. Various substituted thiochroman-4-one derivatives have been synthesized by an efficient method. The synthesized compounds 7a–y and 8a–t were evaluated for their in vitro antifungal activity against the Canidia albicans, Cryptococcus neoformans, Epidermophyton floccosum, Mucor racemosus, Microsporum gypseum and Aspergillus nigerstrain. A series of compounds exhibited significant activity (minimal inhibitory concentrotion (MIC)=0.5–16 µg/mL) against Canidia albicans and Cryptococcus neoformans. The antifungal activity of compound 7b was reached to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the NMT inhibitors. The molecular docking studies revealed an interesting binding profile with very high receptor affinity for NMT of Canidia albicans.