title: Simple and efficient synthesis of 5'-aryl-5'-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities.
abstract: A series of non-hydrolysable 5'-aryl substituted GDP analogs has been synthesized by reacting 5'-azido-5'-deoxyguanosine with different aryl- and benzyloxy-alkynes. Cu(I) nanoparticles in water were found to be the most efficient catalyst, producing the desired 5'-arylguanosines with good yields. The synthesized compounds were screened for in vitro antileishmanial activity against Leishmania donovani axenic amastigotes and intramacrophage amastigotes stages. The 4-(3-nitrobenzyl)-1,2,3-triazole 5'-substituted guanosine analog was found to be the most active in the series with an IC50 of 8.6 μM on axenic amastigotes. Despite a rather low in vitro antileishmanial activity on the intramacrophage amastigotes, the absence of cytotoxicity on RAW 264.7 macrophages justifies further pharmacomodulations making this antileishmanial series promising.
authors.affiliation: BIOCIS - UMR CNRS 8076 Faculté de Pharmacie - Université Paris Sud 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Daligaux
authors.affiliation: BIOCIS - UMR CNRS 8076 Faculté de Pharmacie - Université Paris Sud 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pomel
authors.affiliation: BIOCIS - UMR CNRS 8076 Faculté de Pharmacie - Université Paris Sud 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Leblanc
authors.affiliation: BIOCIS - UMR CNRS 8076 Faculté de Pharmacie - Université Paris Sud 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.affiliation: BIOCIS - UMR CNRS 8076 Faculté de Pharmacie - Université Paris Sud 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France. christian.cave@u-psud.fr.
authors.forename: Christian
authors.identifier: http://orcid.org/0000-0003-0050-6477
authors.initials: C
authors.lastname: Cavé
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry*; D057930:Click Chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology; D008359:Mannose-6-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D011487:Protein Conformation
chemical_list: D000480:Alkynes; D000981:Antiprotozoal Agents; D001386:Azides; C070539:5'-deoxyguanosine; D008359:Mannose-6-Phosphate Isomerase; D003849:Deoxyguanosine
keywords: Antileishmanial activity; Autodock vina; Click reaction; Docking; Guanosine; Leishmania