Antileishmanial Drug Development: A Review of Modern Molecular Chemical Tools and Research Strategies

Author(s): Pavan K. Mantravadi, Anutthaman Parthasarathy, Karunakaran Kalesh*

Journal Name: Current Medicinal Chemistry

Volume 28 , Issue 31 , 2021


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Abstract:

Leishmaniasis, a complex disease caused by at least 20 species of unicellular parasites of the genus Leishmania, disproportionately affects impoverished regions of about 90 tropical and sub-tropical countries. Currently available antileishmanial therapies, particularly for visceral leishmaniasis, are severely limited, with treatment outcome depending on many factors, including the immune status of the patient, comorbidities, malnutrition, and socio-economic conditions in the patient’s geographic location. There is an urgent need for new therapeutics, particularly new effective oral drugs, for visceral leishmaniasis. Despite the availability of the Leishmania genome sequence information and significant research into the biology of the parasites, antileishmanial drug development is hampered by the lack of knowledge about druggable targets in the parasite and difficulties in identifying the molecular targets of compounds that show activity. In this context, we analyzed recent progress in antileishmanial drug development programs, which take advantage of different powerful approaches, such as high-throughput screening of compound libraries, recent developments in genetic methods for assessing essentiality of parasite genes, and chemical, genetic, and proteomics-based target discovery and target validation methods.

Keywords: Leishmaniasis, phenotypic screening, target-based screening, CRISP/Cas9, cosmid library, proteasome, N-myristoylation, cyclin-dependent kinase.

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Article Details

VOLUME: 28
ISSUE: 31
Year: 2021
Published on: 25 November, 2020
Page: [6337 - 6357]
Pages: 21
DOI: 10.2174/0929867328666201125121018
Price: $65

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