Part II of the review describes biological activities of nucleosides modified in
the position 2’ and/or 3’ of a sugar moiety including 2’- and/or 3’-deoxy, 2’,3’-dideoxydidehydro
and 2’-β-C-methylated derivatives. Analogues with a changed configuration
in the sugar residue and others sugar modifications will be a subject of
the part III of the review. Together with the part I it would be a short but possibly
comprehensive review of nucleosides’ biological activities. In the group of analogues
modified in the position 2’ and/or 3’ of the sugar moiety the following derivatives
among others are listed: AZT (zidovudine) – one of the key nucleoside reverse transcriptase
inhibitors (NRTI), which are the core of highly active antiretroviral therapy
(HAART) against virus HIV; didanosine (ddI) – another potent NRTI with medical
importance; stavudine – FDA approved NRTI; zalcitabine – historically important
NRTI, however, because of a high mitochondrial toxicity is no longer in use;
puromycin – a wide spectrum antibiotic which causes premature chain termination
during translation, isolated from Streptomyces alboniger; gemcitabine – chemotherapy
medication developed by Eli Lilly and Company and used to treat ovarian,
breast, pancreas, bladder cancer and non-small cell lung carcinoma; cordycepin
– the most intriguing analogue extracted from Cordyceps sp. known to traditional
Chinese medicine (TCM) for centuries, possessing multi-activity against different
cancer types; cladribine – used in the treatment of chronic lymphocytic leukemia,
cutaneous T-cell lymphoma, hairy cell leukemia and non-Hodgkin’s lymphomas;
valopicitabine – a prodrug form of 2’-C-methylcytidine, which was a promising
HCV treatment agent, however, it was held during clinical trials and finally sofosbuvir
developed by M.J. Sofia from Pharmasset Inc.– a ProTide prodrug form of
2’-deoxy-2’-fluoro-β-C-methyluridine 5’-monosphate, which revolutionized HCV
infection therapy.
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