Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Miltefosine analogues with comparable antileishmanial activity and significantly reduced macrophage cytotoxicity
Δημιουργός/Συγγραφέας:	Alonso, Lais Lemes, Laís Flávia Nunes [EL] Μαγουλάς, Γιώργος[EN] Magoulas, George Costa, Brenda de Lucena Gomes, Rodrigo Saar Dorta, Miriam Leandro Bolognesi, Maria Laura Romeiro, Luiz Antonio Soares [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Alonso, Antonio
Ημερομηνία:	2025
Γλώσσα:	Αγγλικά
ISSN:	1678-8060 0074-0276
DOI:	10.1590/0074-02760240219
Άλλο:	40435100
Περίληψη:	BACKGROUND Miltefosine (MIL) is the only oral drug approved for leishmaniasis treatment, but its use is limited by gastrointestinal toxicity. Novel alkylphospholipid analogues may provide safer and more effective alternatives. OBJECTIVES This study aimed to assess the antileishmanial activity, cytotoxicity, and membrane interactions of three MIL analogues TC387, TC388, and TC437 against Leishmania amazonensis. METHODS Antileishmanial and cytotoxic activities were evaluated in L. amazonensis, J774.A1 macrophages, and erythrocytes. Membrane interactions were characterized using spin-label electron paramagnetic resonance (EPR) spectroscopy. FINDINGS TC387, TC388, and TC437 demonstrated EC50 values of 10-16 µM for intracellular amastigotes, compared to 17 µM for MIL, with selectivity indices (SI) ranging from 43-163, significantly higher than MIL’s SI of 5. EPR data revealed that the analogues increased membrane protein dynamics and caused greater disruption at the lipid-protein interface of parasite membranes relative to MIL. This disruption likely enhances pore formation, ion leakage, and reactive oxygen species (ROS) production, leading to parasite death. MAIN CONCLUSIONS The MIL analogues TC387, TC388, and TC437 exhibited superior SI and comparable or slightly enhanced antileishmanial activity relative to MIL, along with very low hemolytic potential. These findings support further investigation of these analogues as promising oral therapeutic candidates for leishmaniasis.
Τίτλος πηγής δημοσίευσης:	Memorias do Instituto Oswaldo Cruz
Τόμος/Κεφάλαιο:	120
Θεματική Κατηγορία:	[EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Βιοχημεία[EN] Biochemistry [EL] Φασματοσκοπία[EN] Spectroscopy [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	miltefosine analogues Leishmania macrophage erythrocytes electron paramagnetic resonance
Όροι και προϋποθέσεις δικαιωμάτων:	Open access article.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1590/0074-02760240219
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο