Aktywność biologiczna modyfikownych nukleozydów. Część 2
Journal Title: Wiadomości Chemiczne - Year 2018, Vol 72, Issue 5
Abstract
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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Maurycy Szlenkier
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