title: Synthesis and antifungal activities of novel 2-aminotetralin derivatives.
abstract: Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14alpha-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.
authors: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors: Bin
authors: B
authors: Yao
authors: Haitao
authors: H
authors: Ji
authors: Yongbin
authors: Y
authors: Cao
authors: Youjun
authors: Y
authors: Zhou
authors: Jü
authors: J
authors: Zhu
authors: Jiaguo
authors: J
authors: Lü
authors: Yaowu
authors: Y
authors: Li
authors: Jun
authors: J
authors: Chen
authors: Canhui
authors: C
authors: Zheng
authors: Yuanying
authors: Y
authors: Jiang
authors: Rongmei
authors: R
authors: Liang
authors: Hui
authors: H
authors: Tang
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010088:Oxidoreductases / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D058886:Sterol 14-Demethylase; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014623:Vaginal Diseases / Q000188:drug therapy
chemical_list: D000935:Antifungal Agents; C548418:CYP51A1 protein, human; C548417:Cyp51 protein, rat; D013764:Tetrahydronaphthalenes; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase