New 4-methoxy-naphthalene derivatives as promisor antifungal agents for paracoccidioidomycosis treatment

被引：11

作者：

Bagatin, Mariane C. ^{[1
]}

Rozada, Andrew M. F. ^{[1
]}

Rodrigues, Franciele A. V. ^{[2
]}

Bueno, Paulo S. A. ^{[3
]}

Santos, Jessyka L. ^{[4
]}

Canduri, Fernanda ^{[4
]}

Kioshima, Erika S. ^{[2
]}

Seixas, Flavio A. V. ^{[3
]}

Basso, Ernani A. ^{[1
]}

Gauze, Gisele F. ^{[1
]}

机构：

[1] Univ Estadual Maringa, Dept Chem, Maringa, PR, Brazil

[2] Univ Estadual Maringa, Dept Clin Anal & Biomed, Maringa, PR, Brazil

[3] Univ Estadual Maringa, Dept Technol, Umuarama, PR, Brazil

[4] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP, Brazil

来源：

FUTURE MICROBIOLOGY | 2019年 / 14卷 / 03期

关键词：

antifungal activity; carbohydrazide; homoserine dehydrogenase; molecular modeling; MOLECULAR-DYNAMICS;

D O I：

10.2217/fmb-2018-0276

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Aim: Novel 4-methoxy-naphthalene derivatives were synthesized based on hits structures in order to evaluate the antifungal activity against Paracoccidioides spp. Methods: Antifungal activity of compounds was evaluated against P. brasiliensis and most promising compounds 2 and 3 were tested against eight clinically important fungal species. Results: Compound 3 was the more active compound with MIC 8 to 32g.ml(-1) for Paracoccidioides spp without toxicity monkey kidney and murine macrophagecells. Carbohydrazide 3 showed good synergistic antifungal activity with amphotericin B against P. brasiliensis specie. Titration assay of carbohydrazide 3 with PbHSD enzyme demonstrates the binding ligand-protein. Molecular dynamics simulations show that ligand 3 let the PbHSD protein more stable. Conclusion: New carbohydrazide 3 is an attractive lead for drug development to treat paracoccidioidomycoses.

引用

页码：235 / 246

页数：12

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