Synthesis and In Vitro Biocompatibility Studies of Novel Alkoxy 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes

Abstract

BODIPYs are bicyclic aromatic compounds with unique spectroscopic, photophysical, and chemical properties. This study aimed to find BODIPYs with characteristics biocompatible with human cell lines for possible use as imaging agents. Six BODIPY derivatives were synthesised with groups linked to boron, fluorine, phenol, or catechol, resulting in compounds with different physicochemical characteristics. NMR, absorption, and emission spectroscopy and mass spectrometry were subsequently used to characterise them. Afterwards, the biocompatibility of these compounds was evaluated using MTT, SRB, and cellular uptake assays in A549 and H1299 cell lines. Furthermore, a haemolysis assay was performed on human blood cells. To summarise the main results, BODIPYs 1 to 4 showed considerable fluorescence. In contrast, BODIPYs 5 and 6 showed very weak fluorescence, which could be related to the presence of the catechol group and its quenching properties. Regarding biocompatibility, all compounds had metabolic activity and viability above 80% and 70%, respectively. BODIPYs 3 and 6 presented the most consistent data, demonstrating good uptake and, in general, haemolytic activity below 25%. In conclusion, the cytotoxic effects of the compounds were not considerable, and the presence of cyclic alkoxides in BODIPYs 3 and 6 may introduce exciting features that should be highlighted for dual imaging for BODIPY 3 due to its fluorescence or for radioactive labelling in the case of both BODIPYs.