Synergistic combination of alkylphosphocholines with peptaibols in targeting Leishmania infantum in vitro

Publication date: August 2018Source: International Journal for Parasitology: Drugs and Drug Resistance, Volume 8, Issue 2Author(s): Irene Fragiadaki, Anna Katogiritis, Theodora Calogeropoulou, Hans Brückner, Effie ScoulicaAbstractAnti-leishmanial treatment increasingly encounters therapeutic limitations due to drug toxicity and development of resistance. The effort for new therapeutic strategies led us to work on combinations of chemically different compounds that could yield enhanced leishmanicidal effect. Peptaibols are a special type of antimicrobial peptides that are able to form ion channels in cell membranes and potentially affect cell viability. We assayed the antileishmanial activity of two well studied helical peptaibols, the 16-residue antiamoebin and the 20-residue alamethicin-analogue suzukacillin, and we evaluated the biological effect of their combination with the alkylphosphocholine miltefosine and its synthetic analogue TC52. The peptaibols tested exhibited only moderate antileishmanial activity, however their combination with miltefosine had a super-additive effect against the intracellular parasite (combination index 0.83 and 0.43 for antiamoebin and suzukacillin respectively). Drug combinations altered the redox stage of promastigotes, rapidly dissipated mitochondrial membrane potential and induced concatenation of mitochondrial network promoting spheroidal morphology. These results evidenced a potent and specific antileishmanial effect of the peptaibols/m...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research