Synthesis, in vitro Antifungal Activity and Molecular Modeling Studies of New Mannich Bases Derived from Lawsone

被引：18

作者：

Allochio Filho, Joao F. ^{[1
]}

Roldi, Larissa L. ^{[1
]}

Delarmelina, Maicon ^{[1
]}

Fiorot, Rodolfo G. ^{[1
]}

Andrade, Jessica T. ^{[2
]}

Aleixo, Alan A. ^{[2
]}

Carvalho, Rafaella S. ^{[2
]}

Araujo, Marcelo G. F. ^{[2
]}

Ferreira, Jaqueline M. S. ^{[2
]}

Taranto, Alex G. ^{[3
]}

Romao, Wanderson ^{[4
]}

Greco, Sandro J. ^{[1
]}

机构：

[1] Univ Fed Espirito Santo, Dept Quim, Lab Sintese Organ & Med, Ave Ferrari 514, BR-29075910 Vitoria, ES, Brazil

[2] Univ Fed Sao Joao Del Rei, Microbiol Lab, Campus Ctr Oeste, BR-35501296 Divinopolis, MG, Brazil

[3] Univ Fed Sao Joao Del Rei, Lab Quim Farmaceut Med, Campus Ctr Oeste, BR-35501296 Divinopolis, MG, Brazil

[4] Univ Fed Espirito Santo, Dept Quim, Lab Petr, Ave Ferrari 514, BR-29075910 Vitoria, ES, Brazil

来源：

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY | 2016年 / 27卷 / 11期

关键词：

lawsone; Mannich bases; antifungal activity; docking; BIOLOGICAL EVALUATION; CANDIDA-ALBICANS; DRUG DESIGN; DERIVATIVES; ANTIBACTERIAL; DOCKING; AMINONAPHTHOQUINONES; NAPHTHOQUINONES; EPIDEMIOLOGY; OPTIMIZATION;

D O I：

10.5935/0103-5053.20160104

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Hydroxynaphthoquinones such as lawsone (2-hydroxy-1,4-naphthoquinone) have proven to be effective antifungal agents. These compounds were tested for antifungal activity against yeast standard and clinical strains by the broth microdilution method. Among the synthetic lawsone derivatives, 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl) methyl) naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl) amino)(phenyl) methyl) naphthalene-1,4-dione and 2-hydroxy-3(( 2-hydroxyphenyl)((4-nitrophenyl) amino) methyl) naphthalene-1,4-dione showed high activity against Candida albicans ATCC 10231, with minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs) ranging from 20 to 330 and from 80 to 330 mu g mL(-1), respectively. Moreover, they also showed a mechanism of action on exogenous ergosterol. Therapeutic concentrations (CC50) of 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl) methyl) naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl) amino)(phenyl) methyl) naphthalene-1,4-dione and 2-hydroxy-3-((2-hydroxyphenyl)((4-nitrophenyl) amino) methyl) naphthalene-1,4-dione were 52.81, 52.58 and 85.94 mu g mL(-1), respectively, which can be considered moderate or low. In addition, docking studies showed that these compounds had similar binding energy to standard ketoconazole, which are recognized as the molecular target by van der Waals interactions. Furthermore, they are under Lipinski's rule of 5 with a druglikeness score better than ketoconazole and nystatin. These findings suggest that 2-hydroxy-3-((2-hydroxyphenyl)(pyrrolidin-1-yl) methyl) naphthalene-1,4-dione, 2-hydroxy-3-(((4-nitrophenyl) amino)(phenyl) methyl) naphthalene-1,4dione and 2-hydroxy-3-((2-hydroxyphenyl)((4-nitrophenyl) amino) methyl) naphthalene-1,4-dione have potential as leading compounds against human fungal infections.

引用

页码：2127 / 2140

页数：14

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