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Design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors
S Manfredini1, P G Baraldi, E Durini
1Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. mv9@dns.unfie.it
Bioorganic & Medicinal Chemistry Letters
|June 8, 2001
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.