Explorando o potencial farmacológico de dissacarídeos de carragenanas como agentes antitumorais: uma abordagem in sílico

Abstract

Carrageenans, sulfated galactans, have antitumor activity that can be enhanced by their depolymerization. This means that their oligosaccharides, including disaccharides, being less structurally complex, may have pharmacological potential in the treatment of various tumors. However, it is still unknown whether these disaccharides/oligosaccharides are pharmacologically viable and by what mechanisms they act to inhibit tumor growth. Therefore, the objective of this study was to utilize bioinformatics tools to investigate the pharmacological properties and potential molecular targets of disaccharides most representative of iota, kappa, and lambda carrageenans. To achieve this, the pharmacokinetic profile and drug-like physicochemical properties of disaccharides were initially predicted. Subsequently, the molecular targets of these disaccharides were predicted, and among them, those that are already targets of oncological drugs were selected. Molecular docking was then conducted to evaluate the binding capacity and affinity between the selected targets and disaccharides. For comparative analysis of binding energies, oncological drugs acting on these targets were also subjected to docking. In general, disaccharides exhibited favorable metabolization, excretion, and toxicity profiles, but they face permeability challenges in biological membranes, affecting their absorption and distribution. Furthermore, they met most of the physicochemical criteria proposed in drug similarity tests, except for polarity and lipophilicity, which were below and above the desirable limits, respectively. In the selection of molecular targets, five common targets were predicted: carbonic anhydrases (CAs) I, II, IX, XII, and XIV, which are already targeted by several oncological drugs. In docking, the binding energies were similar or superior to those of drugs already used for these targets. Regarding the interactions between disaccharides and CAs, those involving the zinc cofactor stood out, as it is the primary mechanism for inhibiting these enzymes. These findings indicate a promising avenue for carrageenan disaccharides as cancer therapeutics.