In VitroandIn VivoStudies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis
ABSTRACTCarbaporphyrin ketals are porphyrinoid compounds in which a pyrrole ring of a typical porphyrin macrocycle has been replaced by a ketal-substituted indene ring. It was recently demonstrated that these compounds are effectivein vitroagainstLeishmania tarentolae. Theirin vitroeffectiveness is increased when they are exposed to visible light; they act as photosensitizers capable of mediating the production of reactive oxygen species (ROS). Following on this evidence, the effectiveness and cytotoxicity of the dimethyl and diethyl carbaporphyrin ketals (CKOMe and CKOEt, respectively) were determinedin vitrousing pathogenicLeishmaniaspecies with and without exposure to visible light (2 and 4 h). The effectiveness against various pathogenicLeishmaniaspecies was determined to be in a micromolar range. Additionally, the effect of encapsulating the carbaporphyrin ketals in liposome formulations was tested. Liposomal delivery diminished their toxicity, while the effectiveness was enhanced upon exposure to visible light (photodynamic effect). The cytotoxicity levels for human U937 cells and hamster peritoneal macrophages were in the ranges of 0.3 to 9 μM and 7 to 330 μM, respectively. When testedin vivo, using a hamster (Mesocricetus auratus) model of cutaneous leishmaniasis, CKOMe was active even in the dark, suggesting that the compound, once metabolized in the animal tissue, produces an active ingredient that does not seem to be photosensitive. Reduction in lesion size, histopathologic analyses, and smears confirmed thein vivo effectiveness of the compound, since the parasitic load was diminished without noticeable toxic effects.