Next generation imidazothiazole and imidazooxazole derivatives as potential drugs against brain-eating amoebae.
Brain infection
Brain-eating amoebae
Drugs
Human cell
Therapy
Treatment
Journal
Parasitology research
ISSN: 1432-1955
Titre abrégé: Parasitol Res
Pays: Germany
ID NLM: 8703571
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
12
03
2024
accepted:
29
05
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
12
6
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38864931
doi: 10.1007/s00436-024-08255-5
pii: 10.1007/s00436-024-08255-5
doi:
Substances chimiques
Thiazoles
0
Antiprotozoal Agents
0
Imidazoles
0
Oxazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
241Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Akbar N, Siddiqui R, Iqbal M, Sagathevan K, Kim KS, Habib F, Khan NA (2021) Gut bacteria of Rattus rattus (rat) produce broad-spectrum antibacterial lipopeptides. ACS Omega 6:12261–12273. https://doi.org/10.1021/acsomega.1c01137
Akbar N, Kaman WE, Sarink M, Nazmi K, Bikker FJ, Khan NA, Siddiqui R (2022) Novel Antiamoebic Tyrocidine-Derived Peptide against Brain-Eating Amoebae. ACS Omega 7:28797–28805. https://doi.org/10.1021/acsomega.2c01614
doi: 10.1021/acsomega.2c01614
pubmed: 36033708
pmcid: 9404165
Akbar N, Siddiqui R, El-Gamal MI, Zaraei S-O, Alawfi BS, Khan NA (2023) The anti-amoebic potential of carboxamide derivatives containing sulfonyl or sulfamoyl moieties against brain-eating Naegleria fowleri. Parasitol Res. https://doi.org/10.1007/s00436-023-07953-w
Butt CG (1966) Primary Amebic Meningoencephalitis. N Engl J Med 274:1473–1476. https://doi.org/10.1056/NEJM196606302742605
doi: 10.1056/NEJM196606302742605
pubmed: 5939846
Cárdenas-Zúñiga R, Silva-Olivares A, Villalba-Magdaleno JDA, Sánchez-Monroy V, Serrano-Luna J, Shibayama M (2017) Amphotericin B induces apoptosis-like programmed cell death in Naegleria fowleri and Naegleria gruberi. Microbiology 163:940–949. https://doi.org/10.1099/mic.0.000500
doi: 10.1099/mic.0.000500
pubmed: 28721850
Cope JR, Ali IK (2016) Primary Amebic Meningoencephalitis: What Have We Learned in the Last 5 Years? Curr Infect Dis Rep 18:31. https://doi.org/10.1007/s11908-016-0539-4
doi: 10.1007/s11908-016-0539-4
pubmed: 27614893
pmcid: 5100007
De Jonckheere JF (2011) Origin and evolution of the worldwide distributed pathogenic amoeboflagellate Naegleria fowleri. Infect Genet Evol 11:1520–1528. https://doi.org/10.1016/j.meegid.2011.07.023
doi: 10.1016/j.meegid.2011.07.023
pubmed: 21843657
Debnath A (2021) Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads. Expert Rev Anti Infect Ther 19:1099–1106. https://doi.org/10.1080/14787210.2021.1882302
doi: 10.1080/14787210.2021.1882302
pubmed: 33496193
pmcid: 8410612
Debnath A, Tunac JB, Galindo-Gómez S, Silva-Olivares A, Shibayama M, McKerrow JH (2012) Corifungin, a New Drug Lead against Naegleria, Identified from a High-Throughput Screen. Antimicrob Agents Chemother 56:5450–5457. https://doi.org/10.1128/AAC.00643-12
doi: 10.1128/AAC.00643-12
pubmed: 22869574
pmcid: 3486592
Ellis D (2002) Amphotericin B: spectrum and resistance. J Antimicrob Chemother 49:7–10. https://doi.org/10.1093/jac/49.suppl_1.7
doi: 10.1093/jac/49.suppl_1.7
pubmed: 11801575
Grace E, Asbill S, Virga K (2015) Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options. Antimicrob Agents Chemother 59:6677–6681. https://doi.org/10.1128/AAC.01293-15
doi: 10.1128/AAC.01293-15
pubmed: 26259797
pmcid: 4604384
Griffin JL (1972) Temperature Tolerance of Pathogenic and Nonpathogenic Free-Living Amoebas. Science 178:869–870. https://doi.org/10.1126/science.178.4063.869
doi: 10.1126/science.178.4063.869
pubmed: 5085984
Güémez A, García E (2021) Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments. Biomolecules 11:1320. https://doi.org/10.3390/biom11091320
doi: 10.3390/biom11091320
pubmed: 34572533
pmcid: 8469197
Klein R, Nagy O, Tóthová C, Chovanová F (2020) Clinical and Diagnostic Significance of Lactate Dehydrogenase and Its Isoenzymes in Animals. Vet Med Int 2020:1–11. https://doi.org/10.1155/2020/5346483
doi: 10.1155/2020/5346483
Król-Turmińska K, Olender A (2017) Human infections caused by free-living amoebae. Ann Agric Environ Med 24:254–260. https://doi.org/10.5604/12321966.1233568
doi: 10.5604/12321966.1233568
pubmed: 28664704
Ma P, Visvesvara GS, Martinez AJ, Theodore FH, Daggett P-M, Sawyer TK (1990) Naegleria and Acanthamoeba Infections: Review. Clin Infect Dis 12:490–513. https://doi.org/10.1093/clinids/12.3.490
doi: 10.1093/clinids/12.3.490
Maclean Rebecca C, Richardson Dennis J, LePardo R, Marciano-Cabral F (2004) The identification of Naegleria fowleri from water and soil samples by nested PCR. Parasitol Res 93(3):211–217. https://doi.org/10.1007/s00436-004-1104-x
Martinez AJ, Visvesvara GS (1997) Free-living, Amphizoic and Opportunistic Amebas. Brain Pathol 7:583–598. https://doi.org/10.1111/j.1750-3639.1997.tb01076.x
doi: 10.1111/j.1750-3639.1997.tb01076.x
pubmed: 9034567
Mesa-Arango AC, Montiel-Ramos J, Zapata B, Durán C, Betancur-Galvis L, Stashenko E (2009) Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity. Mem Inst Oswaldo Cruz 104:878–884. https://doi.org/10.1590/S0074-02762009000600010
doi: 10.1590/S0074-02762009000600010
pubmed: 19876560
Moseman EA (2020) Battling brain-eating amoeba: Enigmas surrounding immunity to Naegleria fowleri. PLOS Pathog 16:e1008406. https://doi.org/10.1371/journal.ppat.1008406
doi: 10.1371/journal.ppat.1008406
pubmed: 32324819
pmcid: 7179828
Oh Y-H, Jeong S-R, Kim J-H, Song K-J, Kim K, Park S, Sohn S, Shin H-J (2005) Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody. Parasite Immunol 27:453–459. https://doi.org/10.1111/j.1365-3024.2005.00799.x
doi: 10.1111/j.1365-3024.2005.00799.x
pubmed: 16255744
Park J-H, El-Gamal MI, Lee YS, Oh C-H (2011) New imidazo[2,1-b]thiazole derivatives: Synthesis, in vitro anticancer evaluation, and in silico studies. Eur J Med Chem 46:5769–5777. https://doi.org/10.1016/j.ejmech.2011.08.024
doi: 10.1016/j.ejmech.2011.08.024
pubmed: 22033063
Pugh JJ, Levy RA (2016) Naegleria fowleri : diagnosis, pathophysiology of brain inflammation, and antimicrobial treatments. ACS Chem Neurosci 7:1178–1179. https://doi.org/10.1021/acschemneuro.6b00232
Shahin AI, Zaib S, Zaraei S-O, Kedia RA, Anbar HS, Younas MT, Al-Tel TH, Khoder G, El-Gamal MI (2023) Design and synthesis of novel anti-urease imidazothiazole derivatives with promising antibacterial activity against Helicobacter pylori. PLoS ONE 18:e0286684. https://doi.org/10.1371/journal.pone.0286684
Shehata MK, Uzair M, Zaraei S, Shahin AI, Shah SJA, Ullah S, Iqbal J, El-Gamal MI (2023) Synthesis, biological evaluation, and molecular modeling studies of a new series of imidazothiazole or imidazooxazole derivatives as inhibitors of ectonucleoside triphosphate diphosphohydrolases (NTPDases). Med Chem Res 32:314–325. https://doi.org/10.1007/s00044-022-03000-y
doi: 10.1007/s00044-022-03000-y
Siddiqui R, Ali IKM, Cope JR, Khan NA (2016) Biology and pathogenesis of Naegleria fowleri. Acta Trop 164:375–394. https://doi.org/10.1016/j.actatropica.2016.09.009
Siddiqui R, El-Gamal MI, Sajeev S, Zaraei S-O, Khan NA (2023) Novel anti-Acanthamoebic properties of raloxifene sulfonate/sulfamate derivatives. Mol Biochem Parasitol 256:111582. https://doi.org/10.1016/j.molbiopara.2023.111582
doi: 10.1016/j.molbiopara.2023.111582
pubmed: 37562558
Soltow SM, Brenner GM (2007) Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. Antimicrob Agents Chemother 51:23–27. https://doi.org/10.1128/AAC.00788-06
Van De Voorde H, De Jonckheere J (1977) The Distribution of Naegleria Fowleri in Man-Made Thermal Waters. Am J Trop Med Hyg 26:10–15. https://doi.org/10.4269/ajtmh.1977.26.10
doi: 10.4269/ajtmh.1977.26.10
pubmed: 842770
Vargas-Zepeda J, Gómez-Alcalá AV, Vázquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F (2005) Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin. Arch Med Res 36:83–86. https://doi.org/10.1016/j.arcmed.2004.11.003
Yoder JS, Eddy BA, Visvesvara GS, Capewell L, Beach MJ (2010) The epidemiology of primary amoebic meningoencephalitis in the USA, 1962–2008. Epidemiol Infect 138:968–975. https://doi.org/10.1017/S0950268809991014
doi: 10.1017/S0950268809991014
pubmed: 19845995