Journal article
Targeting Mitochondrial Functions as Antimalarial Regime, What Is Next?
Current clinical microbiology reports, v 4(4)
01 Dec 2017
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose of Review Malaria parasites continue to demonstrate their ability to evolve drug resistance, underscoring the need to maintain a long-term program of antimalarial drug development. The parasite mitochondrion is an essential organelle in every lifecycle stage. In the parasite, there are similar to 300 proteins encoded on the nuclear genome destined for the mitochondrion (around 6% of the genome), plus 3 protein genes present on the 6-kb mitochondrial genome. Many of these gene products compose pathways that are critical for the mitochondrion and the mitochondrial contribution to the parasite. The mitochondrial electron transport chain (mtETC) is essential for the parasite and has been validated as an antimalarial drug target. Another mitochondrially located target is the parasite dihydroorotate dehydrogenase (DHODH), which is involved in the essential pyrimidine biosynthesis pathway. In this review, we will summarize recent advancements in drug development targeting the mtETC and DHODH. We will also discuss other pathways within the mitochondrion that hold promise for future exploitation in the search for additional antimalarial drug targets.
Recent Findings Recent drug development efforts have advanced two compounds into clinical evaluation, ELQ-300 and DSM265, targeting the mtETC and DHODH, respectively. These compounds are very potent against malaria parasites at multiple lifecycle stages and have shown good pharmacological properties such as long half-lives and metabolic stability. However, progress toward the development of antimalarial compounds against other mitochondrial functions has been very limited.
Summary New drugs that target the mtETC and DHODH are likely to reach the clinic in the near future. Additional studies are required to verify the essentiality of other mitochondrial pathways in malaria parasites and validate novel antimalarial drug targets needed to help ensure the continuing future development of new antimalarial drugs.
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Details
- Title
- Targeting Mitochondrial Functions as Antimalarial Regime, What Is Next?
- Creators
- Hangjun Ke - Drexel UniversityMichael W. Mather - Drexel University
- Publication Details
- Current clinical microbiology reports, v 4(4)
- Publisher
- Springer Nature
- Number of pages
- 17
- Grant note
- AI028398 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000455400100001
- Scopus ID
- 2-s2.0-85047905920
- Other Identifier
- 991019169595704721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Microbiology