Contribution to the drug development of natural and hemi-synthetic triterpenic esters as antiparasitic drugs
In: boreal:265388;; (2022)
Online
Hochschulschrift
Zugriff:
Malaria and Neglected Tropical Diseases such as Human African Trypanosomiasis (HAT) and leishmaniasis still remain nowadays a global healthcare concern and the severe therapeutic limitations and resistance threats make crucial the research for innovative drugs. Given the antiparasitic potential of pentacyclic triterpenic esters, hemi-synthesis of new derivatives, ADME profile analysis and formulation design were explored on selected promising compounds. The selected compounds were a mixture of C-27 natural triterpenic esters (8TTE) isolated from the twigs of Keetia leucantha, and the C-3 hemi-synthetic ester, ursolic acid 3-O-phenyl propionate (UAOPP), both effective in vitro and in vivo against malaria and HAT, respectively. Bioisosters of UAOPP were also hemi-synthesized using one step synthesis. The stability profiles in biological environments and metabolic analysis of the lead compounds were investigated with a validated analytical method. To improve their bioavailability, specific bioactive triterpenic esters’ formulations were designed and tested for the in vitro antiparasitic activity and intestinal absorption/permeability using a validated more sensitive analytical method. This work contributes to the bioactive triterpenic esters development both from natural and (hemi-)synthetic sources as orally active antiparasitic drugs. ; Le paludisme et les maladies tropicales négligées telles que la trypanosomiase humaine africaine (THA) et la leishmaniose restent encore de nos jour un problème de santé mondial et les limitations thérapeutiques sévères et l'apparition de résistances rendent cruciale la recherche de médicaments innovants. Compte tenu du potentiel antiparasitaire des esters triterpéniques pentacycliques, l'hémi-synthèse de nouveaux dérivés, l'analyse du profil ADME et la conception de formulations ont été explorées sur des composés prometteurs sélectionnés. Les composés sélectionnés étaient un mélange d'esters triterpéniques naturels en C-27 (8TTE) isolé des tiges de ...
Titel: |
Contribution to the drug development of natural and hemi-synthetic triterpenic esters as antiparasitic drugs
|
---|---|
Autor/in / Beteiligte Person: | Schioppa, Laura ; UCL - SSS/LDRI - Louvain Drug Research Institute ; UCL - Faculté de pharmacie et des sciences biomédicales ; Quetin-Leclercq, Joëlle ; Muccioli, Giulio ; Frederich, Michel ; Mingeot-Leclercq, Marie-Paule ; Evrard, Brigitte ; Sahpaz, Sevser |
Link: | |
Quelle: | boreal:265388;; (2022) |
Veröffentlichung: | 2022 |
Medientyp: | Hochschulschrift |
Sonstiges: |
|