Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Magoulas, GE (Author) Other; Afroudakis, P (Author) Other; Georgikopoulou, K (Author) Other; Roussaki, M (Author) Other; Borsari, C (Author) Other; Fotopoulou, T (Author) Other; Santarem, N (Author) Other; Barrias, E (Author) Other; Nevado, PT (Author) Other; Hachenberg, J (Author) Other; Bifeld, E (Author) Other; Ellinger, B (Author) Other; Kuzikov, M (Author) Other; Fragiadaki, I (Author) Other; Scoulica, E (Author) Other; Clos, J (Author) Other; Gul, S (Author) Other; Costi, MP (Author) Other; de Souza, W (Author) Other; Prousis, KC (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Calogeropoulou, T (Author) Other

Journal

Title: Molecules

Vol. 65

Final page: 4204

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00V-8GC

DOI: 10.3390/molecules26144204

Abstract (EN): 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 mu M. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 37