Nowadays, improvement of physicochemical, biopharmaceutical and pharmacokinetic
properties of pharmacologically active compounds is connected with
development of prodrugs. Prodrugs are defined as pharmaceutical compounds
inactive in their parent form and converted either chemically or enzymatically to
the active derivative in the organism. A lot of prodrugs are aromatic compounds
because of benzene ring reactivity. There are two main classes of prodrugs. In the
carrier-linked prodrugs, the active drug is linked to a carrier through bioreversible
covalent bond removed by enzymatic or chemical reactions. The second class comprises
bioprecursor prodrugs that are modified in the body to induce the functional
groups. Additionally, based on the site of prodrugs conversion into their active
forms, they are classified into two groups: prodrugs metabolized intracellulary and
prodrugs metabolized extracellulary. Chemical or enzymatic transformation of prodrugs
may occur through their reduction, decarboxylation, oxidative deamination,
cyclization, phosphorylation and/or hydrolysis. These reactions enable to overcome
different barriers in drug delivery through changes in aqueous solubility, chemical
instability and insufficient oral adsorption. It may also cause prolonged duration of
drug action. Moreover, the prodrugs strategy allows achieving brain and tumor specific
targeting. Summarizing, the designing of the prodrugs seems to be one of the
most promising strategies to enhance the therapeutic effect of drugs and reduction
of their negative side effects.
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