Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo |
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| Affiliation: | 1. Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 prosp. Oktyabrya, 450075 Ufa, Russian Federation;2. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse, 57, CH-4002 Basel, Switzerland;3. University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland;1. School of Material Science and Engineering, Henan University of Technology, Zhengzhou, Henan 450001, China;2. School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China;1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;2. School of Life Sciences, Central South University, Changsha 410013, China;1. Department of Chemistry, College of Sciences, University of Sharjah, Sharjah, PO Box 27272, United Arab Emirates;2. National Centre for Advanced Tribology at Southampton, Department of Mechanical Engineering, University of Southampton, Highfield, Southampton, SO17 1BJ, United Kingdom;3. Electrochemical Engineering Laboratory and Materials Engineering Research Group, Engineering Sciences, University of Southampton, Highfield, Southampton, SO17 1BJ, United Kingdom;1. Institut de Chimie des Substances Naturelles (ICSN-CNRS) UPR2301, Gif-sur-Yvette Cedex, France;2. Centre d’Etude et de Recherche Médecins d’Afrique (CERMA), 43, rue des Glycines, 91600 Savigny sur Orge, France;3. CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205, route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France;4. Centre de Biochimie Structurale (CBS), UMR 5048 CNRS/UM1- 554 Inserm/UM1, Montpellier Cedex, France;5. Université de Toulouse III, UPS, INPT, F-31077 Toulouse cedex 4, France |
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| Abstract: | We studied the antischistosomal activity of betulin, betulinic acid and its 9 triphenylphosphonium derivatives characterized by a covalently linkage of the hydrophobic fragment of triterpenoid at C(2)- or C(30)-position with the triphenylphosphonium moiety via a hydrocarbon bridge. The triphenylphosphonium salts showed in vitro antischistosomal activity against newly transformed schistosomula (NTS) and adult worms of Schistosoma mansoni at low micromolar concentrations. In contrast betulin and betulinic acid were inactive against NTS and adult S. mansoni. Of the 9 triphenylphosphonium derivatives tested, the allyl salts 10 (IC50 of 0.76 μg/mL) and 11 (IC50 of 0.64 μg/mL) demonstrated the highest antischistosomal activity against adult S. mansoni. Low worm burden reductions of 22% were observed in vivo for these two compounds. In conclusion, triphenylphosphonium derivatives were obtained from available natural betulin by simple transformations, rendering it practical and useful for large scale application. However, further structural modifications are necessary to translate the promising antischistosomal in vitro activities into in vivo. |
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| Keywords: | Betulin Betulinic acid Triphenylphosphonium compounds In vitro In vivo |
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