Next generation imidazothiazole and imidazooxazole derivatives as potential drugs against brain-eating amoebae.

Autor: Akbar N; Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, 27272, UAE., Siddiqui R; Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University Edinburgh, Edinburgh, EH14 4AS,, UK.; Microbiota Research Center, Istinye University, Istanbul, 34010, Turkey., El-Gamal MI; Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, 27272, UAE.; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, UAE., Khan NA; Microbiota Research Center, Istinye University, Istanbul, 34010, Turkey. naveed5438@gmail.com., Zaraei SO; Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, 27272, UAE., Saeed BQ; Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, 27272, UAE.; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, UAE., Alharbi AM; Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia., Dash NR; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, UAE.
Jazyk: angličtina
Zdroj: Parasitology research [Parasitol Res] 2024 Jun 12; Vol. 123 (6), pp. 241. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1007/s00436-024-08255-5
Abstrakt: Managing primary amoebic meningoencephalitis, induced by Naegleria fowleri poses a complex medical challenge. There is currently no specific anti-amoebic drug that has proven effectiveness against N. fowleri infection. Ongoing research endeavours are dedicated to uncovering innovative treatment strategies, including the utilization of drugs and immune modulators targeting Naegleria infection. In this study, we explored the potential of imidazo[2,1-b]thiazole and imidazooxazole derivatives that incorporate sulfonate and sulfamate groups as agents with anti-amoebic properties against N. fowleri. We assessed several synthesized compounds (1f, 1m, 1q, 1s, and 1t) for their efficacy in eliminating amoebae, their impact on cytotoxicity, and their influence on the damage caused to human cerebral microvascular endothelial (HBEC-5i) cells when exposed to the N. fowleri (ATCC 30174) strain. The outcomes revealed that, among the five compounds under examination, 1m, 1q, and 1t demonstrated notable anti-parasitic effects against N. fowleri (P ≤ 0.05). Compound 1t exhibited the highest anti-parasitic activity, reducing N. fowleri population by 80%. Additionally, three compounds, 1m, 1q, and 1t, significantly mitigated the damage inflicted on host cells by N. fowleri. However, the results of cytotoxicity analysis indicated that while 1m and 1q had minimal cytotoxic effects on endothelial cells, compound 1t caused moderate cytotoxicity (34%). Consequently, we conclude that imidazo[2,1-b]thiazole and imidazooxazole derivatives containing sulfonate and sulfamate groups exhibit a marked capacity to eliminate amoebae viability while causing limited toxicity to human cells. In aggregate, these findings hold promise that could potentially evolve into novel therapeutic options for treating N. fowleri infection.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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