Drug screening using shape-based virtual screening and in vitro experimental models of cutaneous Leishmaniasis

Article


Cardoso Santos, C., Meuser Batista, M., Inam Ullah, A., Rama Krishna Reddy, T. and Soeiro, M. de N. C. 2021. Drug screening using shape-based virtual screening and in vitro experimental models of cutaneous Leishmaniasis. Parasitology. 148 (1), p. 98–104. https://doi.org/10.1017/S0031182020001900
AuthorsCardoso Santos, C., Meuser Batista, M., Inam Ullah, A., Rama Krishna Reddy, T. and Soeiro, M. de N. C.
Abstract

Cutaneous leishmaniasis (CL) is one of the most disregarded tropical neglected disease with the occurrence of self-limiting ulcers and triggering mucosal damage and stigmatizing scars, leading to huge public health problems and social negative impacts. Pentavalent antimonials are the first-line drug for CL treatment for over 70 years and present several drawbacks in terms of safety and efficacy. Thus, there is an urgent need to search for non-invasive, non-toxic and potent drug candidates for CL. In this sense, we have implemented a shape-based virtual screening approach and identified a set of 32 hit compounds. In vitro phenotypic screenings were conducted using these hit compounds to check their potential leishmanicidal effect towards Leishmania amazonensis (L. amazonensis). Two (Cp1 and Cp2) out of the 32 compounds revealed promising antiparasitic activities, exhibiting considerable potency against intracellular amastigotes present in peritoneal macrophages (IC₅₀ values of 9.35 and 7.25 μm, respectively). Also, a sterile cidality profile was reached at 20 μm after 48 h of incubation, besides a reasonable selectivity (≈8), quite similarly to pentamidine, a diamidine still in use clinically for leishmaniasis. Cp1 with an oxazolo[4,5-b]pyridine scaffold and Cp2 with benzimidazole scaffold could be developed by lead optimization studies to enhance their leishmanicidal potency.

JournalParasitology
Journal citation148 (1), p. 98–104
ISSN0031-1820
Year2021
PublisherCambridge University Press
Accepted author manuscript
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Anyone
Digital Object Identifier (DOI)https://doi.org/10.1017/S0031182020001900
Publication dates
Online07 Oct 2020
PrintJan 2021
Publication process dates
Accepted07 Oct 2020
Deposited19 Apr 2021
Copyright holder© The Author(s) 2020.
Copyright informationThis article has been published in a revised form in Parasitology https://doi.org/10.1017/S0031182020001900. This version is published under a Creative Commons CC-BY-NC-ND. No commercial re-distribution or re-use allowed. Derivative works cannot be distributed.
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