In vitro models in drug discovery and development for leishmaniasis: A perspective
The intracellular Leishmania amastigote model (ILAM) has been instrumental in advancing drug discovery for leishmaniasis treatment over the past 40 years. This review explores the evolution and current applications of ILAMs in screening and drug development, focusing on its advantages for testing dr...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2025-06-01
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| Series: | Annals of Medical Science and Research |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/amsr.amsr_51_24 |
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| Summary: | The intracellular Leishmania amastigote model (ILAM) has been instrumental in advancing drug discovery for leishmaniasis treatment over the past 40 years. This review explores the evolution and current applications of ILAMs in screening and drug development, focusing on its advantages for testing drug efficacy against intracellular amastigotes. Early models relied on macrophage cell lines, with notable progress made in the 2000s through molecular biology techniques such as bioluminescent and fluorescent transfection, enabling high-throughput screening (HTS) of large compound libraries. This method identified crucial drug leads, contributing to the extensive screening of over 4.5 million compounds by organizations such as the Drugs for Neglected Diseases initiative (DNDi). Recent advances in transfection technologies and CRISPR-Cas9 have further refined the potential of ILAM, allowing more precise genetic manipulation to assess parasite survival and drug resistance. Despite these advancements, challenges remain in maintaining Leishmania virulence in culture and addressing the variation in drug susceptibility across species. Furthermore, complex in vitro models and pharmacokinetic–pharmacodynamic (PK-PD) studies are being explored to optimize drug regimens and improve the predictive power of these models. While ILAMs have become a standard in drug discovery, their integration with more complex models and medicinal chemistry remains crucial for progressing toward an effective, short-course, oral treatment for all forms of leishmaniasis. |
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| ISSN: | 2949-785X 2949-7868 |