title: Evaluation of the activity of new cationic carbosilane dendrimers on trophozoites and cysts of Acanthamoeba polyphaga.
abstract: Dendrimers are repetitively branched molecules with a broad spectrum of applications, mainly for their antimicrobial properties and as nanocarriers for other molecules. Recently, our research group have synthesized and studied their activity against Acanthamoeba sp., causative agent of a severe ocular disease in humans: Acanthamoeba keratitis. New cationic carbosilane dendrimers were tested against the protozoa forms at different concentrations and for different incubation times. Trophozoite viability was determined by manual counting and cyst viability by observing excystment in microplates with fresh culture medium. Cytotoxicity was checked on HeLa cells using the microculture tetrazolium assay. Alterations were observed by optical microscopy and by flow cytometry staining with propidium iodide. Six out of the 18 dendrimers tested were non-cytotoxic and effective against the trophozoite form, having one of them (dendrimer 14 with an IC50 of 2.4 + 0.1 mg/L) a similar activity to chlorhexidine digluconate (IC50 1.7 + 0.1 mg/L). This dendrimer has a polyphenoxo core and a sulphur atom close to the six -NH3+ terminal groups. On the other hand, only two dendrimers showed some effect against cysts (dendrimers 14 and 17). However, their minimum cysticidal concentrations were cytotoxic and less effective than the control drug. The alterations on the amoeba morphology produced by the treatment with dendrimers were size reduction, increased complexity, loss of acanthopodia and cell membrane disruption. In conclusion, these results suggest that some dendrimers may be studied in animal models to test their effect and that new dendrimers with similar features should be synthesized.
authors.affiliation: Departamento de Biomedicina y Biotecnología, Universidad de Alcalá, Alcalá de Henares, Spain, irene.heredero@edu.uah.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Heredero-Bermejo
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Copa-Patiño
authors.forename: Juan
authors.initials: J
authors.lastname: Soliveri
authors.forename: Elena
authors.initials: E
authors.lastname: Fuentes-Paniagua
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: Rafael
authors.initials: R
authors.lastname: Gomez
authors.forename: Jorge
authors.initials: J
authors.lastname: Perez-Serrano
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects*; D015823:Acanthamoeba Keratitis / Q000188:drug therapy* / Q000469:parasitology; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003261:Contact Lenses / Q000469:parasitology; D003470:Culture Media; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology*; D053058:Trophozoites / Q000187:drug effects
chemical_list: D000891:Anti-Infective Agents, Local; D003470:Culture Media; D050091:Dendrimers; D012821:Silanes; C504072:carbosilane; C010882:chlorhexidine gluconate; D002710:Chlorhexidine