Amoebicidal activity of cationic carbosilane dendrons derived with 4-phenylbutyric acid against Acanthamoeba griffini and Acanthamoeba polyphaga trophozoites and cysts

Abstract

Amoebae from the genus Acanthamoeba are important pathogens responsible for severe illnesses in humans such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. In the last few decades, AK diagnoses have steadily increased. Most patients suffering from AK were contact lens users and the infection was related to poor hygiene. However, therapy is not yet well established, and treatments may last for several months due to resistance. Moreover, these treatments have been described to generate cytotoxicity. Therefore, there is an urgent need to develop new therapeutic strategies against AK. In this study, the amoebicidal activity of different generation cationic carbosilane dendrons derived with 4-phenylbutyric acid was demonstrated against Acanthamoeba polyphaga and Acanthamoeba griffini trophozoites and cysts. In addition, the combination of chlorhexidine digluconate and the most effective dendron (ArCO2G2(SNMe3I)4) showed an in vitro effect against Acanthamoeba trophozoites and cysts, reducing the minimal trophozoite amoebicidal concentration as well as concentrations with cysticidal activity.

Carbosilane dendritic nanostructures, highly versatile platforms for pharmaceutical applications

“…One of the pathologies where CBS dendrimers have been evaluated as amoebicidal agents is acanthamoeba keratitis—a severe ocular disease in humans caused by Acanthamoeba polyphaga . CBS dendrimers (Figure S5) decorated with guanidine or biguanide moieties (Heredero‐Bermejo et al, 2018; Martin‐Perez et al, 2019) and cationic carbosilane dendrons derived from 4‐phenylbutyric acid (Figure S4; López‐Barona et al, 2022) caused a cytoplasmic damage in both trophozoites and cysts forms, including vacuolization, depletion of cytoplasmic contents, and reduced cell size. The multivalency of dendritic systems can play two different roles.…”