Photosensitizers for photodynamic therapy: Structure-activity analysis of cyanine dyes through design of experiments

In this work, a new series of pentamethine indolenine cyanine dyes has been designed and synthesized with the aim to investigate a structure-activity relationship on their photodynamic activity. The heteroaromatic indolenine ring has been differently functionalized (no substituents, bromine, iodine, and carboxylic acid) to determine the effect of the substitution on the ROS production, cytotoxicity, photodynamic activity, and cellular uptake. A statistical multivariate design such as the Design of Experiments (DoE) has been applied to evaluate which factor greatly affects the cyanine photoactive behavior, maximizing the information content, precision, and accuracy in the results, while keeping the number of experiments low. All the synthesized dyes present low cytotoxicity in the dark, but only some of them are able to promote a phototoxic effect, upon irradiation, in MCF-7 cell lines, confirming a structure-activity relationship.