Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Design, synthesis and antiparasitic evaluation of click phospholipids
Δημιουργός/Συγγραφέας:	Magoulas, George E Afroudakis, Pantelis Georgikopoulou, Kalliopi Roussaki, Marina Borsari, Chiara Fotopoulou, Theano Santarem, Nuno Barrias, Emile Tejera Nevado, Paloma Hachenberg, Julia Bifeld, Eugenia Ellinger, Bernhard Kuzikov, Maria Fragiadaki, Irini Scoulica, Effie Clos, Joachim Gul, Sheraz Costi, Maria Paola de Souza, Wanderley [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos Cordeiro da Silva, Anabela [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora
Εκδότης:	MDPI
Ημερομηνία:	2021-07-10
Γλώσσα:	Αγγλικά
ISSN:	1420-3049
DOI:	10.3390/molecules26144204
Άλλο:	34299479
Περίληψη:	A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure-activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.
Τίτλος πηγής δημοσίευσης:	Molecules (Basel, Switzerland) Special Issue: Advances of Medicinal Chemistry against Kinetoplastid Protozoa (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) Infections: Drug Design, Synthesis and Pharmacology)
Τόμος/Κεφάλαιο:	26
Τεύχος:	14
Σελίδες:	4204
Θεματική Κατηγορία:	[EL] Μικροβιολογία[EN] Microbiology [EL] Χημική τεχνολογία[EN] Chemical technolgy [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Βιοχημεία[EN] Biochemistry [EL] Περιβαλλοντική υγεία[EN] Environmental health
Λέξεις-Κλειδιά:	Leishmania donovani Leishmania infantum Trypanosoma brucei Trypanosoma cruzi Antiparasitic activity Ether phospholipids Heterocyclic rings Antiparasitic Agents Chagas Disease Click Chemistry Humans Leishmania Leishmaniasis Macrophages Phospholipids Structure-Activity Relationship Trypanosoma cruzi Drug Design
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2021 by the Authors. Licensee MDPI, Basel, Switzerland.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/1420-3049/26/14/4204
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.mdpi.com/journal/molecules
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο