» Articles » PMID: 34211341

New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection

Abstract

The spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti- agents are urgently needed. This study explored new series of imidazoles for anti- properties and . The imidazoles showed moderate to strong and specific action against growth of . For example, the efficacy of the imidazole compounds to restrict growth was ≥ 12-fold specific towards relative to the mammalian cells. Additionally, the study revealed that the imidazoles exhibited promising anti- efficacy corroborating the anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards and the oral LD in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.

Citing Articles

Ingestion of Fluids of the Ocular Surface Containing Eye Drops of Imidazole Derivatives-Alpha Adrenergic Receptor Agonists as Paragons.

Sosa I Pharmaceuticals (Basel). 2024; 17(6).

PMID: 38931425 PMC: 11206365. DOI: 10.3390/ph17060758.

References
1.
Gupta S, Igoillo-Esteve M, Michels P, Cordeiro A . Glucose-6-phosphate dehydrogenase of trypanosomatids: characterization, target validation, and drug discovery. Mol Biol Int. 2011; 2011:135701. PMC: 3196259. DOI: 10.4061/2011/135701. View

2.
Deeks E . Fexinidazole: First Global Approval. Drugs. 2019; 79(2):215-220. DOI: 10.1007/s40265-019-1051-6. View

3.
. Control and surveillance of African trypanosomiasis. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1999; 881:I-VI, 1-114. View

4.
Adeyemi O, Eseola A, Plass W, Otuechere C, Elebiyo T . New imidazoles cause cellular toxicity by impairing redox balance, mitochondrial membrane potential, and modulation of HIF-1α expression. Biochem Biophys Res Commun. 2020; 529(1):23-27. DOI: 10.1016/j.bbrc.2020.05.059. View

5.
Pelfrene E, Harvey Allchurch M, Ntamabyaliro N, Nambasa V, Ventura F, Nagercoil N . The European Medicines Agency's scientific opinion on oral fexinidazole for human African trypanosomiasis. PLoS Negl Trop Dis. 2019; 13(6):e0007381. PMC: 6597029. DOI: 10.1371/journal.pntd.0007381. View