title: Design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors.
abstract: Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhibitory activity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. mv9@dns.unfie.it
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.forename: P G
authors.initials: PG
authors.lastname: Baraldi
authors.forename: E
authors.initials: E
authors.lastname: Durini
authors.forename: L
authors.initials: L
authors.lastname: Porcu
authors.forename: A
authors.initials: A
authors.lastname: Angusti
authors.forename: S
authors.initials: S
authors.lastname: Vertuani
authors.forename: N
authors.initials: N
authors.lastname: Solaroli
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: A
authors.initials: A
authors.lastname: Karlsson
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000037:antagonists & inhibitors
chemical_list: D001087:Arabinonucleosides; D004791:Enzyme Inhibitors; D014764:Viral Proteins; C105339:thymidine kinase 2; D013937:Thymidine Kinase