Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design, synthesis and bioactive evaluation

被引：49

作者：

Fang, Xian-Fu ^{[1
]}

Li, Di ^{[1
]}

Tangadanchu, Vijai Kumar Reddy ^{[1
,2
]}

Gopala, Lavanya ^{[1
,3
]}

Gao, Wei-Wei ^{[1
]}

Zhou, Cheng-He ^{[1
]}

机构：

[1] Southwest Univ, Sch Chem & Chem Engn, Key Lab Appl Chem Chongqing Municipal, Inst Bioorgan & Med Chem, Chongqing 400715, Peoples R China

[2] Indian Inst Chem Technol, CSIR, Hyderabad 500007, Andhra Prades, India

[3] Sri Venkateswara Univ, Tirupati, Andhra Prades, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 22期

基金：

中国国家自然科学基金;

关键词：

5-Flucytosine; Fluconazole; Antifungal; Molecular modeling; Quantum chemical studies; DNA; CALF THYMUS DNA; BIOLOGICAL EVALUATION; ANTIMICROBIAL EVALUATION; 2-AMINOTHIAZOLYL QUINOLONES; AZOLE COMPOUNDS; METAL-IONS; ANTIBACTERIAL; AGENTS; FLUCYTOSINE; RESISTANCE;

D O I：

10.1016/j.bmcl.2017.10.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel potentially antifungal hybrids of 5-flucytosine and fluconazole were designed, synthesized and characterized by H-1 NMR, C-13 NMR, IR and HRMS spectra. Bioactive assay manifested that some prepared compounds showed moderate to good antifungal activities in comparison with fluconazole and 5-flucytosine. Remarkably, the 3,4-dichlorobenzyl hybrid 7h could inhibit the growth of C. albicans ATCC 90023 and clinical resistant strain C. albicans with MIC values of 0.008 and 0.02 mM, respectively. The active molecule 7h could not only rapidly kill C. albicans but also efficiently permeate membrane of C. albicans. Molecular docking study revealed that compound 7h could interact with the active site of CACYP51 through hydrogen bond. Quantum chemical studies were also performed to explain the high antifungal activity. Further preliminary mechanism research suggested that molecule 7h could intercalate into calf thymus DNA to form a steady supramolecular complex, which might block DNA replication to exert the powerful bioactivities. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：4964 / 4969

页数：6

共 58 条

[1] Design, synthesis, and biological evaluation of novel carbazole aminothiazoles as potential DNA-targeting antimicrobial agents [J].