Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.
| Autor: | Ferrins L; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Buskes MJ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Kapteyn MM; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States., Engels HN; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States., Enos SE; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States.; Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States., Lu C; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States., Klug DM; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Singh B; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Quotadamo A; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States.; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy., Bachovchin K; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Tear WF; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Spaulding AE; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Forbes KC; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Bag S; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Rivers M; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., LeBlanc C; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Burchfield E; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Armand JR; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Diaz-Gonzalez R; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Ceballos-Perez G; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., García-Hernández R; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Pérez-Moreno G; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Bosch-Navarrete C; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Ruiz-Pérez LM; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Gamarro F; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., González-Pacanowska D; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Navarro M; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Mensa-Wilmot K; Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA, United States., Pollastri MP; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, United States., Kyle DE; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States., Rice CA; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States.; Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in microbiology [Front Microbiol] 2023 May 10; Vol. 14, pp. 1149145. Date of Electronic Publication: 2023 May 10 (Print Publication: 2023). |
| DOI: | 10.3389/fmicb.2023.1149145 |
| Abstrakt: | Acanthamoeba species, Naegleria fowleri , and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d ( A. castellanii EC Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ferrins, Buskes, Kapteyn, Engels, Enos, Lu, Klug, Singh, Quotadamo, Bachovchin, Tear, Spaulding, Forbes, Bag, Rivers, LeBlanc, Burchfield, Armand, Diaz-Gonzalez, Ceballos-Perez, García-Hernández, Pérez-Moreno, Bosch-Navarrete, Ruiz-Pérez, Gamarro, González-Pacanowska, Navarro, Mensa-Wilmot, Pollastri, Kyle and Rice.) |
| Databáze: | MEDLINE |
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