Síntese e caracterização de derivados indirubinicos contendo unidades de carboidratos, potenciais agentes anticâncer

Abstract

Indirubin is an alkaloid belonging to the class of natural indigos extracted from the secondary metabolites of plants such as Polygonum Tinctorium, commonly used in Chinese medicine as a source of drugs. Natural indigos are recognized for their industrial application as dyes and pigments, and in addition, they have various biological activities such as antiviral, antifungal and especially anticancer action, so indirubin is a promising prototype for new drugs. However, despite having several biological applications, some strategies are needed to overcome problems related to its low bioavailability and improve its physicochemical properties, such as the insertion of hydrophilic portions linked to the original skeleton. Thus, combining the original indirubin skeleton with carbohydrates together with pharmacophoric groups such as the triazole ring has proved to be a viable alternative for the development of new drugs for anticancer therapies. In this sense, this dissertation evaluated the possibility of direct coupling of indirubin with carbohydrate units via the Sn2 reaction. However, the results obtained were not satisfactory, so it was decided to use the click reaction to obtain indirubin derivatives containing sugar units. To this end, two synthesis routes were evaluated using the click reaction: the first route started with previously functionalized isatin, which was then subjected to the aldol condensation reaction with 3-acetoxindol, and the second route involved the propargylation of indirubin for the subsequent click reaction.The first synthethic route proved to be more promising compared to the second synthetic route, and the failure to obtain propargylated indirubin in the second route was the determining step for excluding the route in question. The loss of selectivity of the reaction was investigated by computational calculations which are in good agreement with the experimental results