Computer-aided Molecular Design of Dye-based Photosensitizers for Photodynamic Therapy

Photosensitizers are used in Photodynamic therapy (PDT) to treat various medical ailments including cancer, acne vulgaris, skin and organ diseases, bacterial infections, and sexually transmitted diseases. When photons of necessary and specific wavelengths interact with photosensitizers, reactive oxygen species (ROS) are generated which damage the cellular structure of the infected tissue - inducing cellular necrosis and lysis or apoptosis. Ideal photosensitizers have a high quantum yield of singlet and triplet oxygen which damages the infected cells. Computer-aided molecular design (CAMD) was employed in order to search for new photosensitizers with such desirable traits. Quantitative structure-property relationships (QSPR's) were defined based on 21 different known photosensitizer structures for properties, singlet oxygen quantum yield and molar extinction coefficient. Connectivity indices were used as molecular descriptors to develop QSPRs. Correlations were obtained by linear regression. Chemical moieties were then analyzed, processed, and recombined using combinatorial optimization techniques in order to develop new photosensitizers. The optimization formulation minimizes the difference between the properties of the newly built photosensitizer and the target value and it is solved stochastically using the Tabu Search algorithm. Novel candidate photosensitizers have been proposed here for future research and use in PDT.