Synthesis and Structural Characterization of Novel Dimers of Dipyridothiazine as Promising Antiproliferative Agents

Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC₅₀ and the selectivity index SI. The most active derivative, 4c, showed an IC₅₀ activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.