Synthesis and photodynamic activity of a panel of BODIPY dyes

Eight difluoro-bora-diaza-s-indacenes (BODIPY dyes) were synthesized and characterized for their physicochemical properties. The photoxicity of these photosensitizers (PSs) was assessed on the human colon carcinoma cell line HCT116. To elucidate some aspects of the PS-induced phototoxicity, flow cytometric analysis of the percentage of apoptotic and autophagic cells was performed . [Display omitted] ► Synthesis and photodynamic activity of a panel of eight BODIPYs (PSs). ► Physico-chemical data about singlet oxygen, fluorescence and lipophilicity. ► Nano-molar IC50 values photo induced killing effect against HCT116 cell line. ► The most efficient PS was exploited against MCF7, A2780 and A2780/CP8 cell lines. Eight BODIPY dyes were synthesized and used as photosensitizers (PSs) on the human colon carcinoma cell line HCT116. In this panel of molecules, the structure varies in the substituents on pyrrole 2, 6 positions and on the phenyl ring at the indacene 8 position. For these compounds relevant physico-chemical parameters, such as singlet oxygen production, fluorescent quantum yield, absorbance profile and a relative rank of lipophilicity were determined. Our results indicate that some of these novel PSs are very effective in reducing the growth/viability of HCT116 cells when irradiated with a green LED source, whereas they are practically devoid of activity in the dark, up to 5μM. To evaluate whether cell death is induced under these conditions, flow cytometric analysis of the percentage of apoptotic and autophagic cells was performed on four molecules, chosen for their efficacy/structural characteristics. Our data indicate that phototoxicity likely occurs mainly through apoptotic cell death, whereas autophagy seems to play a minor role in determining cell fate. Furthermore, the relationship between singlet oxygen generation and the PS efficacy is confirmed, thus underscoring the importance of the heavy-atom effect and of the presence of an aryl substituent at dipyrromethene 8 (meso) position. Among the PSs here described, the most efficient BODIPY was successfully tested on three other human cancer cell lines of different tissue origin, MCF7 (breast), A2780 and A2780/CP8 (ovary, sensitive and resistant to cisplatin, respectively), yielding IC50 values comparable to those obtained on HCT116.