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Febrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection

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dc.contributor.authorPandey, Rajan Kumar
dc.contributor.authorOjha, Rupal
dc.contributor.authorDevender, Moodu
dc.contributor.authorSebastian, Prince
dc.contributor.authorNamdeo, Madhulika
dc.contributor.authorKumbhar, Bajarang Vasant
dc.contributor.authorSundar, Shyam
dc.contributor.authorMaurya, Radheshyam
dc.contributor.authorPrajapati, Vijay Kumar
dc.date.accessioned2025-01-27T10:00:58Z
dc.date.available2025-01-27T10:00:58Z
dc.date.issued2022
dc.description.abstractVisceral leishmaniasis (VL) is the deadliest form of leishmaniasis without a safer treatment option. This study implies drug repurposing to find a novel antileishmanial compound, namely febrifugine dihydrochloride (FFG) targeting Leishmania antioxidant system. Starting with virtual screening revealed the high binding affinity and lead likeness of FFG against the trypanothione reductase (TR) enzyme of Leishmania donovani, followed by experimental validation. The promastigotes inhibition assay gave the IC50 concentration of FFG and Miltefosine (positive control) as 7.16 � 1.39 nM and 11.41 � 0.29 ?M, respectively. Their CC50 was found as 451 � 12.73 nM and 135.9 � 5.94 ?M, respectively. FFG has been shown to increase the reactive oxygen species (ROS), leading to apoptosis-like cell death among L. donovani promastigotes. Spleen touch biopsy resulted in 62% and 55% decreased parasite load with FFG and miltefosine treatment, respectively. Cytokine profiling has shown an increased proinflammatory cytokine response post-FFG treatment. Moreover, FFG is safe on the liver toxicity parameter in mice post-treatment. � 2022 Elsevier Inc.
dc.identifier.doihttps://doi.org/10.1016/j.exppara.2022.108250
dc.identifier.issn144894
dc.identifier.urihttps://dl.bhu.ac.in/ir/handle/123456789/13757
dc.publisherAcademic Press Inc.
dc.subjectBALB/c mice
dc.subjectDrug repurposing
dc.subjectFebrifugine
dc.subjectMiltefosine
dc.subjectVisceral leishmaniasis
dc.titleFebrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection
dc.typeArticle
dspace.entity.typePublication
journal.titleExperimental Parasitology
journalvolume.identifier.volume236-237

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2022