Evaluation and synthesis of AZT prodrugs with optimized chemical stabilities: experimental and theoretical analyses

Versatile iron–catechol-based nanoscale coordination polymers with antiretroviral ligand functionalization and their use as efficient carriers in HIV/AIDS therapy

“…Functionalization at this position has already been shown to be successful for the synthesis of AZT prodrugs with chemical and/or enzymatic hydrolysis. 42,43 Afterwards, this ligand, in combination with an iron salt and a bisdentate ligand is used to form the nanoparticles (see Fig 1a). Finally, the release of the drug is expected to take part following a twostep mechanism: I) liberation of the catAZT from the nanoparticle in a pH controlled process and second, liberation of the free AZT drug from the catechol unit in the presence of the corresponding enzymes (see Fig.…”

Stability and plasmatic protein binding of novel zidovudine prodrugs: Targeting site ii of human serum albumin

“…[6,[22][23][24][25] Recently, we reported the synthesis and chemical stability evaluation of three novel prodrugs of AZT obtained by derivatization with different dicarboxylic acids (1-3, Figure 1.c): succinic (1), glutaric (2) and adipic (3) acids. [18] These single prodrugs exhibited adequate chemical stabilities at different pH values (2 -7.4). [18] In order to continue with the development of the above mentioned prodrugs, in the present work we report the design, synthesis and evaluation of the chemical and enzymatic stability of a novel series of AZT double prodrugs obtained by further derivatizing prodrugs 1-3 with a methylated l-phenylalanine moiety (4-6, Figure 1.d).…”

“…[18] These single prodrugs exhibited adequate chemical stabilities at different pH values (2 -7.4). [18] In order to continue with the development of the above mentioned prodrugs, in the present work we report the design, synthesis and evaluation of the chemical and enzymatic stability of a novel series of AZT double prodrugs obtained by further derivatizing prodrugs 1-3 with a methylated l-phenylalanine moiety (4-6, Figure 1.d). In addition, their HSA binding properties were exhaustively studied by combining experimental and theoretical techniques in light of further evaluation of their biopharmaceutical behavior.…”

“…In this way many prodrugs have been prepared by derivatizing the 5´OH of AZT in order to obtain inactive compounds requiring a chemical and/or enzymatic hydrolytic step prior to exhibiting bioactivity.In line with these efforts, we have previously reported the obtention of prodrugs of AZT linking ester and amide moieties at the 5´OH position to obtain both "single" and "double" prodrugs. [14][15][16][18][19][20][21] As an example, oxalic acid (AZT-Ox) was used as linker chain between AZT and different essential aminoacids…”

“…In a first step, prodrugs 1-3 were obtained following our previously reported procedure, [18] after which the synthesis of prodrugs 4-6 was conducted by condensing 1-3…”