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• W2939367718 abstract "Abstract Leishmaniasis is a neglected disease that affects more than 12 million people, with a limited therapy. Plant-derived natural products represent a useful source of anti-protozoan prototypes. In this work, four derivatives were prepared from neolignans isolated from the Brazilian plant Nectandra leucantha , and their effects against intracellular amastigotes of Leishmania ( L .) infantum evaluated in vitro . IC 50 values between 6 and 35 µM were observed and in silico predictions suggested good oral bioavailability, no PAINS similarities, and ADMET risks typical of lipophilic compounds. The most selective (SI > 32) compound was chosen for lethal action and immunomodulatory studies. This compound caused a transient depolarization of the plasma membrane potential and induced an imbalance of intracellular Ca 2+ , possibly resulting in a mitochondrial impairment and leading to a strong depolarization of the membrane potential and decrease of ATP levels. The derivative also interfered with the cell cycle of Leishmania , inducing a programmed cell death-like mechanism and affecting DNA replication. Further immunomodulatory studies demonstrated that the compound eliminates amastigotes via an independent activation of the host cell, with decrease levels of IL-10, TNF and MCP-1. Additionally, this derivative caused no hemolytic effects in murine erythrocytes and could be considered promising for future lead studies." @default.
• W2939367718 created "2019-04-25" @default.
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• W2939367718 date "2019-04-16" @default.
• W2939367718 modified "2023-10-03" @default.
• W2939367718 title "A semi-synthetic neolignan derivative from dihydrodieugenol B selectively affects the bioenergetic system of Leishmania infantum and inhibits cell division" @default.
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• W2939367718 doi "https://doi.org/10.1038/s41598-019-42273-z" @default.
• W2939367718 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6467890" @default.
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