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
Authors | Cardoso Santos, C., Meuser Batista, M., Inam Ullah, A., Rama Krishna Reddy, T. and Soeiro, M. de N. C. |
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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. |
Journal | Parasitology |
Journal citation | 148 (1), p. 98–104 |
ISSN | 0031-1820 |
Year | 2021 |
Publisher | Cambridge University Press |
Accepted author manuscript | License File Access Level Anyone |
Digital Object Identifier (DOI) | https://doi.org/10.1017/S0031182020001900 |
Publication dates | |
Online | 07 Oct 2020 |
Jan 2021 | |
Publication process dates | |
Accepted | 07 Oct 2020 |
Deposited | 19 Apr 2021 |
Copyright holder | © The Author(s) 2020. |
Copyright information | This 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. |
https://repository.uel.ac.uk/item/893qw
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Accepted author manuscript
Dr.Reddy_Parasitology manuscript.pdf | ||
License: CC BY-NC-ND 4.0 | ||
File access level: Anyone |
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