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Design, synthesis, in vitro and in vivo biological evaluation of pyranone-piperazine analogs as potent antileishmanial agents. | LitMetric

Design, synthesis, in vitro and in vivo biological evaluation of pyranone-piperazine analogs as potent antileishmanial agents.

Eur J Med Chem

Molecular Parasitology & Immunology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201 002, India. Electronic address:

Published: October 2021

AI Article Synopsis

Article Abstract

The current therapeutic regimen for visceral leishmaniasis is inadequate and unsatisfactory due to toxic side effects, high cost and emergence of drug resistance. Alternative, safe and affordable antileishmanials are, therefore, urgently needed and toward these we synthesized a series of arylpiperazine substituted pyranone derivatives and screened them against both in vitro and in vivo model of visceral leishmaniasis. Among 22 synthesized compounds, 5a and 5g showed better activity against intracellular amastigotes with an IC of 11.07 μM and 15.3 μM, respectively. In the in vivo, 5a significantly reduced hepatic and splenic amastigotes burden in Balb/c mice model of visceral leishmaniasis. On a mechanistic node, we observed that 5a induced direct Leishmania killing via mitochondrial dysfunction like cytochrome c release and loss of membrane potential. Taken together, our results suggest that 5a is a promising lead for further development of antileishmanial drugs.

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Source
http://dx.doi.org/10.1016/j.ejmech.2021.113516DOI Listing

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