ИСТИНА

The physicochemical properties and biological activity of drug molecules directly depend on functional groups within their structure. The sulfo group is not very often used as a substituent in medicinal chemistry, and its applications are usually related to an improvement in drug solubility. What other opportunities are offered when this functional group is introduced into the molecule structure? To answer this question we have prepared a review of sulfonates described in the literature, among them were drugs, preclinical/clinical development compounds, as well as more than a hundred experimental inhibitors. In some cases sulfo-substituted derivatives can exhibit increased inhibitory activity, improved solubility, reduced toxicity. The negatively charged sulfo group, being a good structural mimetic of carboxyl and phosphate groups, is important for the design of competitive inhibitors of various therapeutic targets, and the esterified sulfo group may be used in the development of prodrugs. We examined more than a hundred complexes of natural and synthetic sulfonates with proteins, deposited in the Protein Data Bank, and analyzed the binding sites of the sulfo group and its interactions with amino acid residues, metal ions, and water molecules. The retrieved structural data and geometric characteristics of hydrogen bonds of the sulfo group may be used in the design of sulfonate-based drug candidates.