Molecules Journal
Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 µM on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.
For details:
Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets
Strahinja Stevanovic 1, Milan Sencanski 1, Mathieu Danel 2, Christophe Menendez 3,4, Roumaissa Belguedj 3,4,5, Abdelmalek Bouraiou 5, Katarina Nikolic 6 , Sandrine Cojean 7, Philippe M. Loiseau 7, Sanja Glisic 1, Michel Baltas 3,4 and Alfonso T. García-Sosa 8
1 Laboratory for Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences VINCA, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia
2 ITAV, Université de Toulouse, CNRS, 31062 Toulouse, France
3 Department of Chemistry, Université de Toulouse, UPS, CNRS UMR 5068, LSPCMIB, 118 Route de Narbonne, 31062 Toulouse, France
4 CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, LSPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse, France
5 Unité de Recherche de Chimie de l’Environnement et Moléculaire Structurale, Université Frères Mentouri, Route de Ain El Bey, 25000 Constantine, Algeria
6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia
7 Antiparasitic Chemotherapy, UMR 8076 CNRS BioCIS, Faculty of Pharmacy Université Paris-Sud, Rue Jean-Baptiste Clément, F 92290 Chatenay-Malabry, France
8 Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia
For more information about Chemspeed solutions:
Molecules 2019, 24, 1282; doi:10.3390/molecules24071282
For details please contact [email protected]