Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis

被引：4
作者：
Sakyi P.O. [1 ,2 ]
Amewu R.K. [1 ]
Devine R.N.O.A. [2 ]
Bienibuor A.K. [2 ]
Miller W.A., III [3 ,4 ,5 ]
Kwofie S.K. [6 ,7 ]
机构：
[1] Department of Chemistry, School of Physical and Mathematical Sciences, College of Basic and Applied Sciences, University of Ghana, PMB LG 56, Legon, Accra
[2] Department of Chemical Sciences, School of Sciences, University of Energy and Natural Resources, Box 214, Sunyani
[3] Department of Medicine, Loyola University Medical Center, Maywood, 60153, IL
[4] Department of Molecular Pharmacology and Neuroscience, Loyola University Medical Center, Maywood, 60153, IL
[5] Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, 19104, IL
[6] Department of Biomedical Engineering, School of Engineering Sciences, College of Basic & Applied Sciences, University of Ghana, PMB LG 77, Legon, Accra
[7] West African Center for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra
来源：
Journal of Parasitic Diseases | 2021年 / 45卷 / 4期
关键词：
Leishmaniasis; Natural product compounds; Ornithine decarboxylase; Sterol biosynthesis; Synthetic compounds; Trypanothione reductase;
D O I：
10.1007/s12639-021-01390-1
中图分类号：
学科分类号：
摘要：
The mortality rate of leishmaniasis is increasing at an alarming rate and is currently second to malaria amongst the other neglected tropical diseases. Unfortunately, many governments and key stakeholders are not investing enough in the development of new therapeutic interventions. The available treatment options targeting different pathways of the parasite have seen inefficiencies, drug resistance, and toxic side effects coupled with longer treatment durations. Numerous studies to understand the biochemistry of leishmaniasis and its pathogenesis have identified druggable targets including ornithine decarboxylase, trypanothione reductase, and pteridine reductase, which are relevant for the survival and growth of the parasites. Another plausible target is the sterol biosynthetic pathway; however, this has not been fully investigated. Sterol biosynthesis is essential for the survival of the Leishmania species because its inhibition could lead to the death of the parasites. This review seeks to evaluate how critical the enzymes involved in sterol biosynthetic pathway are to the survival of the leishmania parasite. The review also highlights both synthetic and natural product compounds with their IC50 values against selected enzymes. Finally, recent advancements in drug design strategies targeting the sterol biosynthesis pathway of Leishmania are discussed. © 2021, Indian Society for Parasitology.
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页码：1152 / 1171
页数：19
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