Targeting pathogenic Acanthamoeba castellanii using DNA minor groove binding agents.

Autor: Alniss HY; College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, 27272 Sharjah, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates. Electronic address: halniss@sharjah.ac.ae., Sajeev S; Research Institute for Medical and Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates., Siddiqui R; Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University Edinburgh EH14 4AS, UK; Microbiota Research Center, Istinye University, Istanbul 34010, Turkey., Daalah M; Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center, Kuwait University, Jabriya, Kuwait., Alawfi BS; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia., Al-Jubeh HM; Research Institute for Medical and Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates., Ravi A; Research Institute for Medical and Health Sciences, University of Sharjah, 27272 Sharjah, United Arab Emirates., Khan NA; Microbiota Research Center, Istinye University, Istanbul 34010, Turkey; School of Science, College of Science and Engineering, University of Derby, Derby DE22 1GB, UK. Electronic address: n.khan2@derby.ac.uk.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2024 Dec; Vol. 260, pp. 107451. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1016/j.actatropica.2024.107451
Abstrakt: DNA minor groove binders exhibit a high degree of sequence specificity and have a variety of biological actions including antiviral, anticancer, antibacterial, and anti-protozoal properties. Since it is the location of non-covalent interactions, the minor groove of double helical B-DNA is gaining significant interest as therapeutic targets. For the purpose of this investigation, the synthesis of five novel DNA minor groove binding agents was accomplished and antiparasitic efficacies were determined against Acanthamoeba castellanii of the T4 genotype in vitro. Using amoebicidal assays, the results revealed that all inhibitors tested showed significant killing of amoebae (P < 0.05). Pre-treatment of amoebae with DNA minor groove binders inhibited parasite-mediated human cell death by measuring lactate dehydrogenase release using cytopathogenicity assays. Cytotoxicity assays revealed minimal effects on human cells. As phenotypic switching leads to infection recurrence, assays revealed that inhibitors blocked amoebae phenotypic transformation. These are promising findings and suggest that DNA minor groove binders may hold promise for further research in the effective eradication of pathogenic A. castellanii.
Competing Interests: Declaration of competing interest Hasan Alniss has a patent pending for MGB compounds. The remaining authors have no conflicts of interest to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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