Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Synergistic combination of alkylphosphocholines with peptaibols in targeting Leishmania infantum in vitro
Δημιουργός/Συγγραφέας:	Fragiadaki I. Katogiritis A. [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Brückner H. Scoulica E.
Εκδότης:	Elsevier Ltd
Ημερομηνία:	2018
Γλώσσα:	Αγγλικά
ISSN:	2211-3207
DOI:	10.1016/j.ijpddr.2018.03.005
Άλλο:	PubMed ID: 29631127
Περίληψη:	Anti-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/miltefosine combinations, achieved with significantly lower concentrations of the compounds compared to monotherapy. Furthermore, they revealed the importance of exploring novel classes of bioactive compounds such as peptaibols and demonstrated for the first time that they can act in synergy with currently used antileishmanial drugs to improve the therapeutic outcome.
Τίτλος πηγής δημοσίευσης:	International Journal for Parasitology: Drugs and Drug Resistance
Τόμος/Κεφάλαιο:	8
Τεύχος:	2
Σελίδες:	194-202
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	Drug synergy Leishmaniasis therapy Miltefosine Mitochondrial membrane potential Peptaibol antibiotics Reactive oxygen species
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2018 The Authors
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	KA 3650; University of Crete, UoC: KA3097. This work was supported by the Special Account for Research Funds of, University of Crete, (SARF UoC) , grand KA3097 . Open access fees were funded by SARF UoC , grand KA 3650 .
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο