Characterization of PfTrxR inhibitors using antimalarial assays and in silico techniques

Chemistry Central Journal

Ranjith Munigunti³  Symon Gathiaka¹  Orlando Acevedo¹  Rajnish Sahu²  Babu Tekwani²  Angela I Calderón³ 

[1] Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, USA

[2] National Center for Natural Products Research & Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, USA

[3] Department of Pharmacal Sciences, 4306 Walker Building, Auburn University, Auburn, AL, USA

关键词: Molecular modeling;    Thioredoxin reductase;    Plasmodium falciparum;    Malaria;   

Others  :  787819
DOI  :  10.1186/1752-153X-7-175

 received in 2013-07-31, accepted in 2013-11-05,  发布年份 2013

【 摘 要 】

Background

The compounds 1,4-napthoquinone (1,4-NQ), bis-(2,4-dinitrophenyl)sulfide (2,4-DNPS), 4-nitrobenzothiadiazole (4-NBT), 3-dimethylaminopropiophenone (3-DAP) and menadione (MD) were tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay and also for analysis of non-covalent interactions with P. falciparum thioredoxin reductase (PfTrxR) through in silico docking studies.

Results

The inhibitors of PfTrxR namely, 1,4-NQ, 4-NBT and MD displayed significant antimalarial activity with IC₅₀ values of < 20 μM and toxicity against 3T3 cell line. 2,4-DNPS was only moderately active. In silico docking analysis of these compounds with PfTrxR revealed that 2,4-DNPS, 4-NBT and MD interact non-covalently with the intersubunit region of the enzyme.

Conclusions

In this study, tools for the identification of PfTrxR inhibitors using phenotyphic screening and docking studies have been validated for their potential use for antimalarial drug discovery project.

【 授权许可】

   
2013 Munigunti et al.; licensee Chemistry Central Ltd.

【 图 表 】

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