<i>Leishmania donovani</i>
            Dipeptidylcarboxypeptidase Inhibitor as a Potential Oral Treatment for Visceral Leishmaniasis

Ramalingam, K.; Gangwar, Sonali; Balodi, Deep Chandra; Anand, Apeksha; Yadav, Shailendra; Biswas, Subhasish; Sasikala, Anil Kumar Karunakaran; Gupta, Kailash C.; Batra, Sanjay; Goyal, Neena

doi:10.1128/aac.02361-21

Cited by 3 publications

(1 citation statement)

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“…It is a poverty‐associated disease which basically affects the poorest of the poor, mainly in developing countries. It is of three types visceral, cutaneous, and mucocutaneous, on that visceral leishmaniasis is a more severe one, if left untreated, it can cause death 1 . This parasite exists in two morphological forms: the promastigote form, which occurs in sand flies and is transmitted to humans by the bite of infected leishmania species, and the amastigote form, which is converted from promastigote in the macrophages of the humans during infection 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Novel chemical scaffold as potential drug against Leishmania donovani: Integrated computational and experimental approaches

Ranjan,

Dubey

2023

J of Cellular Biochemistry

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In this study, we have screened a large number of Food and Drug Administration‐approved compounds for novel anti‐leishmanial molecules targeting the citrate synthase enzyme of the parasite. Based on their docking and molecular dynamic simulation statistics, five compounds were selected. These compounds followed Lipinski's rule of five. Additionally, in vitro, antileishmanial and cytotoxicity studies were performed. The three compounds, Abemaciclib, Bazedoxifene, and Vorapaxar, had shown effective anti‐leishmanial activities with IC50 values of 0.92 ± 0.02, 0.65 ± 0.09, and 6.1 ± 0.91 against Leishmania donovani promastigote and with EC50 values of 1.52 ± 0.37, 2.11 ± 0.38, 10.4 ± 1.27 against intramacrophagic amastigote without significantly harming macrophage cells. Among them, from in silico and antileishmanial activities studies, Abemaciclib had been selected based on their less binding energy, good antileishmanial activities, and also a significant difference in their binding energy with human citrate synthase for cell death mechanistic studies using flow cytometry and a DNA fragmentation assay. The action of this compound resulted in an increased reactive oxygen species production, depolarization of mitochondrial membrane potential, DNA damage, and an increase in the sub‐G1 cell population. These properties are the hallmarks of apoptosis which were further confirmed by apoptotic assay. Based on the above result, this anticancer compound Abemaciclib could be employed as a potential treatment option for leishmaniasis after further confirmation.

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Section: Introductionmentioning

confidence: 99%