Synthesis and antiproliferative activity of thiazole-fused anthraquinones

Abstract

Heterocyclic derivatives of anthraquinone demonstrated a high potential for the development of new antitumor compounds. In this study, we report a scheme for the synthesis of thiazole-fused anthraquinones and the results of their antiproliferative activity. A convenient metal-free method for the thiolation of anthraquinone derivatives has been proposed for the preparation of the key intermediates. C–S bond formation upon nucleophilic substitution of the bromine atom in anthraquinone with 4-methoxybenzyl mercaptan readily occurs under mild conditions using t-BuOK as a base. This process was used for the preparation of anthra[2,3-d]thiazoles with various substituents at position 2, in particular the alkoxycarbonyl group. Study of the chemical properties resulted in the transformation of anthra[2,3-d]thiazole-2-carboxylic acid into a series of carboxamides. Screening the antiproliferative effect revealed moderate activity of compounds 12b and 12d against human cancer cells, showing weaker activity than anthra[2,3-d]thiophene analogs and indicating a crucial role of the heterocyclic nucleus in the antitumor potency of heteroareneanthraquinones.