Novel anti-Acanthamoebic properties of raloxifene sulfonate/sulfamate derivatives

Ruqaiyyah Siddiqui, Mohammed I. El-Gamal, Sreedevi Sajeev, Seyed-Omar Zaraei, Naveed Ahmed Khan

Research output: Contribution to journalArticlepeer-review

Abstract

Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active trophozoite to a resistant cyst form is not well understood; the cyst stage is often resistant to chemotherapy, which is of concern given the rise of contact lens use and the ineffective disinfectants available, versus the cyst stage. Herein, for the first time, a range of raloxifene sulfonate/sulfamate derivatives which target nucleotide pyrophosphatase/phosphodiesterase enzymes, were assessed using amoebicidal and excystation tests versus the trophozoite and cyst stage of Acanthamoeba. Moreover, the potential for cytopathogenicity inhibition in amoebae was assessed. Each of the derivatives showed considerable anti-amoebic activity as well as the ability to suppress phenotypic switching (except for compound 1a). Selected raloxifene derivatives reduced Acanthamoeba-mediated host cell damage using lactate dehydrogenase assay. These findings suggest that pyrophosphatase/phosphodiesterase enzymes may be valuable targets against Acanthamoeba infections.

Original languageEnglish
Article number111582
JournalMolecular and Biochemical Parasitology
Volume256
Early online date9 Aug 2023
DOIs
Publication statusPublished - Dec 2023

Keywords

  • Animals
  • Acanthamoeba castellanii
  • Raloxifene Hydrochloride/pharmacology
  • Sulfonic Acids/pharmacology
  • Trophozoites
  • Alkanesulfonates/pharmacology
  • Phosphoric Diester Hydrolases/pharmacology

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