Evaluation of histone deacetylase inhibitor substituted zinc and indium phthalocyanines for chemo- and photodynamic therapy

In this study, we synthesized and characterized 3-hydroxypyridin-2-thione (3-HPT) bearing zinc (ZnPc-1 and ZnPc-2) and indium (InPc-1 and InPc-2) phthalocyanine (Pc) derivatives, either non-peripherally or peripherally substituted as photosensitizer (PS) agents and evaluated their anti-cancer efficacy on two breast cancer cell lines, MDA-MB-231 and MCF-7 as well as a human endothelial cell line, HUVEC. Our results indicated different localization patterns between ZnPcs and InPcs in addition to enhanced effects on the mitochondrial network for InPcs. Moreover, peripheral or non-peripheral substitution of HDACi moieties altered cellular localization between ZnPc-1 and ZnPc-2, leading to increased IC50 values along with decreased anti-cancer activity for non-peripheral substitution. When considering the compounds' differential effects in vitro, our data indicates that further research is required to determine the ideal Pcs for anti-cancer PDT treatments since the core metals of the compounds have affected the cellular localization, and positioning of the chemotherapeutic residues may inhibit cellular penetrance.

Automated summary

This study synthesized and characterized different Pc derivatives for anti-cancer efficacy, showing varied effects on breast cancer and endothelial cell lines. In particular, InPc derivatives exhibited enhanced effects on the mitochondrial network, while non-peripheral substitutions led to decreased anti-cancer activity. Further research is needed to determine ideal Pc candidates for anti-cancer PDT treatments.