N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter

Alibu, Vincent P.; Daunes, Sylvie; D’Silva, Claudius

doi:10.1016/j.bmcl.2013.05.086

Cited by 5 publications

(2 citation statements)

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“…The L. amazonensis mdr1 gene, which has demonstrated to be 91 and 78% identical to the closely related ldmdr1 gene in L. donovani and lemdr1 gene in L. enriettii , respectively [66, 67], has been shown to be overexpressed in amphotericin B- and Sb-resistant strains of L. donovani [68–70], in a melarsoprol-resistant strain of T. brucei [71, 72] and in benznidazole-resistant epimastigotes of T. cruzi [64, 65]. Otherwise the gene encoding MRPA, which is one of three genes related to drug resistance identified within the H locus and which is amplified in extrachromosomal circles of DNA, was overexpressed in a number of Leishmania strains selected for resistance to Sb III , Sb V or the related metal [15, 73–76].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate

2019

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Background In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis . Methods Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes. Results A total of 723 differentially expressed genes were identified between resistant and sensitive lines. Comparative transcriptomic analysis revealed that genes encoding proteins involved in metabolism (fatty acids) and stress response, as well as those associated with antimony resistance in other Leishmania species, were upregulated in the antimony-resistant line. Most importantly, we observed upregulation of genes encoding autophagy proteins, suggesting that in the presence of trivalent stibogluconate (Sb III ) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites. Conclusions This work identified global transcriptomic changes in an in vitro -adapted strain in response to Sb III . Our results provide relevant information to continue understanding the mechanism used by parasites of the subgenus Leishmania ( L. amazonensis ) to generate an antimony-resistant phenotype. Electronic supplementary material The online version of this article (10.1186/s13071-019-3603-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate

2019

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“…MRP is part of the ABC transporter family and is necessary for some resistance in Trypanosoma species toward trypanocides; particularly ivermectin, melarsoprol, and benznidazole [10,11]. The common MRP gene analyzed from T. brucei species is TbMRPA [12]. To date, there is only one study focused on the MRP Copyright: Nuryady, et al Open Access.…”

Section: Introductionmentioning

confidence: 99%

Multidrug resistance protein structure of Trypanosoma evansi isolated from buffaloes in Ngawi District, Indonesia: A bioinformatics analysis

et al. 2021

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Background and Aim: Trypanosomiasis, also known as surra, is an infectious disease with a wide host spectrum. In Indonesia, this disease is caused by Trypanosoma evansi. Various trypanocidal drugs have been used to treat this pathogen and subsequent disease. Yet, the long-term trypanocidal administration generates drug-resistant T. evansi. Some have identified genetic alterations in T. evansi transporter protein-coding genes that may be responsible for drug resistance. The Multidrug Resistance Protein E (MRPE) gene is a likely candidate gene responsible for the individual resistance. To date, no research has focused on T. evansi MRPE (TevMRPE) in this context. Hence, this research aimed at analyzing and characterizing the TevMRPE gene and protein using a bioinformatics approach. Materials and Methods: T. evansi was isolated from buffalo suffering from surra in Ngawi Regency, Indonesia. Isolated T. evansi was inoculated and cultured in male mice. The T. evansi genome was isolated from mouse blood with a parasitemia degree as high as 105. A polymerase chain reaction procedure was conducted to amplify the putative MRPE coding gene. The amplicon was sequenced and analyzed using MEGA X, BLAST, and I-tasser softwares. Results: The putative TevMRPE coding gene showed sequence similarity as high as 99.79% against the MRPE gene from Trypanosoma brucei gambiense. The protein profile and characteristics depicted that the putative TevMRPE protein was related to a family of Adenosine Triphosphate-Binding Cassette (ABC) transporter proteins. This family of transporter proteins plays a crucial role in the resistance toward several medicines. Conclusion: The obtained gene sequence in this research was identified as the TevMRPE. This gene is homologous to the T. brucei gambiense MRPE gene and possesses ligand active sites for Adenylyl Imidodiphosphate. In addition, MRPE contains enzyme active sites similar to the cystic fibrosis transmembrane conductance regulator. These data suggest that ABC transport proteins, like MRPE, may be necessary to confer trypanocidal drug resistance in T. evansi.

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Antimicrobial effects of N-benzyloxycarbonyl-S-(2,4-dinitrophenyl) glutathione diesters against chloroquinine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum

Daunes

D’Silva

2018

Bioorganic Chemistry

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N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter

Cited by 5 publications

References 22 publications

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate

Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate

Multidrug resistance protein structure of Trypanosoma evansi isolated from buffaloes in Ngawi District, Indonesia: A bioinformatics analysis

Antimicrobial effects of N-benzyloxycarbonyl-S-(2,4-dinitrophenyl) glutathione diesters against chloroquinine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum

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