A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

被引：10

作者：

Borcea, Anca-Maria ^{[1
,2
]}

Marc, Gabriel ^{[1
]}

Ionut, Ioana ^{[1
]}

Vodnar, Dan C. ^{[3
]}

Vlase, Laurian ^{[4
]}

Gligor, Felicia ^{[2
]}

Pricopie, Andreea ^{[1
]}

Pirnau, Adrian ^{[5
]}

Tiperciuc, Brindusa ^{[1
]}

Oniga, Ovidiu ^{[1
]}

机构：

[1] Iuliu Hatieganu Univ Med & Pharm, Dept Pharmaceut Chem, 41 Victor Babes St, Cluj Napoca 400012, Romania

[2] Lucian Blaga Univ Sibiu, Preclin Dept, Pharm Specializat, Fac Med, 2A Lucian Blaga St, Sibiu 550169, Romania

[3] Univ Agr Sci & Vet Med, Dept Food Sci & Technol, 3-5 Manastur St, Cluj Napoca 400372, Romania

[4] Iuliu Hatieganu Univ Med & Pharm, Dept Pharmaceut Technol & Biopharmaceut, 41 Victor Babes St, Cluj Napoca 400012, Romania

[5] Natl Inst Res & Dev Isotop & Mol Technol, 67-103 Donath St, Cluj Napoca 400293, Romania

来源：

MOLECULES | 2019年 / 24卷 / 01期

关键词：

thiazole; anti-Candida; acylhydrazone; lanosterol; 14-demethylase; molecular modeling; ADMET; MICROWAVE-ASSISTED SYNTHESIS; 3,5-DISUBSTITUTED THIAZOLIDINE-2,4-DIONES; MOLECULAR DOCKING; ANTIFUNGAL; DERIVATIVES; ABSORPTION; ADMET;

D O I：

10.3390/molecules24010184

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.

引用

页数：15

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