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Synthesis and in vitro chemical and enzymatic stability of glycosyl 3'-azido-3'-deoxythymidine derivatives as potential anti-HIV agents. 2002

Francesco Bonina, and Carmelo Puglia, and Maria Grazia Rimoli, and Lucia Avallone, and Enrico Abignente, and Giampiero Boatto, and Maria Nieddu, and Rosaria Meli, and Michele Amorena, and Paolo de Caprariis
Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy. boninaf@mbox.unict.it

New glycosyl derivatives of 3'-azido-3'-deoxythymidine (AZT) (1 and 2) were synthesized in order to improve AZT retention in the blood and to guarantee its sustained release, overcoming the necessity of multiple drug administrations. The esters synthesized (1 and 2) link AZT, by a succinyl linker, to the C-3 position of glucose and to C-6 of galactose. Furthermore, the chemical and enzymatic stabilities of esters 1 and 2 were evaluated in order to determine both their stability in aqueous medium and their feasibility to undergo enzymatic cleavage by esterase to regenerate the original drug. The pharmacokinetic profiles of esters 1 and 2, obtained after systemic administration, showed an interesting controlled release, in particular for ester 2, compared to the pharmacokinetic profile of AZT.

UI MeSH Term Description Entries
D008297 Male Males
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D004795 Enzyme Stability The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat. Enzyme Stabilities,Stabilities, Enzyme,Stability, Enzyme
D004950 Esterases Any member of the class of enzymes that catalyze the cleavage of an ester bond and result in the addition of water to the resulting molecules. Esterase
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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