PLASMODIUM FALCIPARUM LACTATE DEHYDROGENASE: AN IMPORTANT DRUG TARGET FOR THE DEVELOPMENT OF NEW ANTIMALARIALS
DOI:
https://doi.org/10.5281/zenodo.17839203Keywords:
Plasmodium Falciparum, Lactate Dehydrogenase (PfLDG), Malaria Treatment, Enzyme Inhibition, Glycolysis, Parasite MetabolismAbstract
Plasmodium falciparum lactate dehydrogenase (PfLDH), a key enzyme in the glycolytic pathway of the malaria parasite, has emerged as a promising drug target due to its essential role in energy generation and its structural differences from human LDH. Several compounds, including natural products like TMDTP from Alstonia boonei, synthetic dihydroxynaphthoic acid analogues, and repurposed drugs such as posaconazole and atorvastatin, have demonstrated significant inhibitory activity against PfLDH. These inhibitors exhibit diverse binding modes and selectivity over human LDH, underscoring the potential of PfLDH as a target for developing new antimalarials with novel mechanisms of action. Continued research and optimization of PfLDH inhibitors are crucial to address the challenge of drug-resistant malaria.
References
I. Atchade PS, Doderer-Lang C, Chabi N, Perrotey S, Abdelrahman T, Akpovi CD, et al. Is a Plasmodium lactate dehydrogenase (pLDH) enzyme-linked immunosorbent (ELISA)-based assay a valid tool for detecting risky malaria blood donations in Africa? Malar J. 2013 Aug;12:279.
II. Wirth JD, Boucher JI, Jacobowitz JR, Classen S, Theobald DL. Functional and Structural Resilience of the Active Site Loop in the Evolution of Plasmodium Lactate Dehydrogenase. Biochemistry. 2018 Nov;57(45):6434–42.
III. Olanlokun JO, Olotu AF, David OM, Idowu TO, Soliman EM, Olorunsogo OO. A novel compound purified from Alstonia boonei inhibits Plasmodium falciparum lactate dehydrogenase and plasmepsin II. J Biomol Struct Dyn. 2019 May;37(8):2193–200.
IV. Sabilil Muttaqin S, Sekar Maji J. Screening of Oxamic Acid Similar 3D Structures as Candidate Inhibitor Plasmodium falciparum L-Lactate Dehydrogenase of Malaria Through Molecular Docking. In: 2018 1st International Conference on Bioinformatics, Biotechnology, and Biomedical Engineering - Bioinformatics and Biomedical Engineering. IEEE; 2018. p. 1–6.
V. Cheung YW, Kwok J, Law AWL, Watt RM, Kotaka M, Tanner JA. Structural basis for discriminatory recognition of Plasmodium lactate dehydrogenase by a DNA aptamer. Proc Natl Acad Sci U S A. 2013 Oct;110(40):15967–72.
VI. Correa R, Coronado L, Caballero Z, Faral P, Robello C, Spadafora C. Extracellular vesicles carrying lactate dehydrogenase induce suicide in increased population density of Plasmodium falciparum in vitro. Sci Rep. 2019 Dec;9(1):5042.
VII. Choi S ryoung, Beeler AB, Pradhan A, Watkins EB, Rimoldi JM, Tekwani B, et al. Generation of Oxamic Acid Libraries: Antimalarials and Inhibitors of Plasmodium falciparum Lactate Dehydrogenase. J Comb Chem. 2007 Mar;9(2):292–300.
VIII. Megnassan E, Keita M, Bieri C, Esmel A, Frecer V, Miertus S. Design of novel dihydroxynaphthoic acid inhibitors of Plasmodium falciparum lactate dehydrogenase. Med Chem. 2012 Sep;8(5):970–84.
IX. Penna-Coutinho J, Cortopassi WA, Oliveira AA, França TCC, Krettli AU. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies. PLoS One. 2011;6(7):e21237.
X. Borah S, Sarma M, Chetia D, Nath D. DESIGN AND SCREENING OF CONESSINE DERIVATIVES TARGETING Pf-LACTATE DEHYDROGENASE IN SEARCH OF NOVEL ANTIMALARIALS: AN IN-SILICO APPROACH. Curr Trends Pharm Res [Internet]. 2024;11(2). Available from: www.dibru.ac.in/ctpr
XI. Biswas P, Roy R, Ghosh K, Nath D, Samadder A, Nandi S. To quest new targets of Plasmodium parasite and their potential inhibitors to combat antimalarial drug resistance. Vol. 48, Journal of Parasitic Diseases. Springer; 2024. p. 671–722.
XII. Ezeala IC, Omeje KO, Ezeala O, Uzor PF, Dim OWF, Anumudu AR, et al. The Inhibitory Potentials of the Root Extract and Fractions of Brenania brieyi (De Wild) (Rubiaceae) on Lactate Dehydrogenase, Phospholipase A2, and α- Amylase in Plasmodium falciparum - Infected Persons. Trends Nat Prod Res. 2024;5(3):129–58.
XIII. Odhar HA, Hashim AF, Humadi SS, Ahjel SW. Ligand-Based Virtual Screening of Fda- Approved Drugs To Identify New Inhibitors Against Lactate Dehydrogenase Enzyme of Malaria Parasites. Int J Appl Pharm. 2024;16(1):255–60.
XIV. Luo W, Yu L, Lu S, Yu Y, Bai Y, Wang S, et al. Design and screening of novel molecular compounds targeting lactate dehydrogenase of Babesia microti. Parasites and Vectors [Internet]. 2025;18(1):1–11. Available from: https://doi.org/10.1186/s13071-024-06623-9
XV. Sama-ae I, Muengthongon P, Tohlaeh A, Rukhachan W, Kiattikul P, Samaeng F, et al. Penicillium‐Derived Inhibitors of Plasmodium falciparum Lactate Dehydrogenase (PfLDH): A Computational Approach for Novel Antimalarial Therapy Development . Scientifica (Cairo). 2025 Jan;2025(1).
XVI. Tremp AZ, Saeed S, Dessens JT. A paternal lactate dehydrogenase critically enhances male gametogenesis and malaria transmission. Sci Rep. 2025;15(1):1–10.
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 International Educational Applied Scientific Research Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
