New world Leishmania spp. infection in people living with HIV: Concerns about relapses and secondary prophylaxis

Araújo, Camila Freire; Oliveira, Iara Barreto Neves; Silva, Muriel Vilela Teodoro; Pereira, Ledice Inácia de Araújo; Pinto, Sebastião Alves; Silveira, Murilo Barros; Dorta, Miriam Leandro; Fonseca, Simone Gonçalves; Gomes, Rodrigo Saar; Ribeiro‐Dias, Fátima

doi:10.1016/j.actatropica.2021.106146

Cited by 2 publications

(1 citation statement)

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“…The most common drugs used for treating leishmaniasis are pentavalent antimonial, amphotericin B, miltefosine, paromomycin, and pentamidine (Chakravarty and Sundar 2019 ; Singh and Kumar 2014 ). However, these drug treatments suffer from one or more limitations, such as treatment failure (Ponte-Sucre et al 2017 ), resistance (Horacio et al 2021 ), longer half-life (Reimao et al 2020 ), relapses after treatment (Araújo et al 2021 ), toxicity (Arenas et al 2017 ), or higher cost (Azim et al 2021 ). Considering the absence of a vaccine, a number of alternative strategies are being researched from a range of significant pathways to create a new drug for the disease (Ranjan et al 2020 ; Vijayakumar et al 2019 ; Vijayakumar and Das 2018 ).…”

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confidence: 99%

In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase

et al. 2022

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In Leishmania sp., the enzymes of de novo cysteine biosynthesis pathway require sulfide. Other organisms utilize sulfide through the sulfide reduction pathway, but Leishmania lacks the gene that encodes these enzymes. Hence, the major source of sulfide for Leishmania is believed to be from the action of 3-mercaptopyruvate sulfurtransferase (3MST) on 3-mercapto-pyruvate (3MP). There has been no effort reported in the past to screen inhibitors against L. donovani 3MST (Ld3MST). As a result, this study examines natural compounds that are potent against Ld3MST and validates it by in vitro activity and cytotoxicity tests. Initially, a library of ~ 5000 natural compounds was subjected to molecular docking approach for screening, and the best hit was validated using a long-term molecular dynamic simulation (MD). Among the docking results, quercetine-3-rutinoside (Rutin) was deemed the best hit. The results of the MD indicated that Rutin was highly capable of interacting with the varied active site segments, possibly blocking substrate access. Additionally, promastigotes and amastigotes were tested for Rutin activity and the IC50 was found to be 40.95 and 90.09 μM, respectively. Similarly, the cytotoxicity assay revealed that Rutin was not toxic even at a concentration of 819.00 μM to THP-1 cell lines. Additionally, the Ld3MST was cloned, purified, and evaluated for enzyme activity in the presence of Rutin. Reduction in the enzyme activity (~ 85%) was observed in the presence of ~ 40 μM Rutin. Thus, this study suggests that Rutin may act as a potent inhibitor of Ld3MST. With further in vivo investigations, Rutin could be a small molecule of choice for combating leishmaniasis. Supplementary Information The online version contains supplementary material available at 10.1007/s00436-022-07532-5.

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