Targeting pathogenic Acanthamoeba castellanii using DNA minor groove binding agents

Hasan Y. Alniss, Sreedevi Sajeev, Ruqaiyyah Siddiqui, Meshal Daalah, Bader S. Alawfi, Hadeel M. Al-Jubeh, Anil Ravi, Naveed A. Khan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number107451
JournalActa Tropica
Volume260
Early online date5 Nov 2024
DOIs
Publication statusPublished - Dec 2024

Keywords

  • Acanthamoeba
  • Cytopathogenicity
  • Cytotoxicity
  • DNA minor groove binders (MGBs)
  • Parasites
  • Treatment

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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