Bisphosphonates-pda: correlation between structure and physicochemical properties

Bisphosphonates are used to treat a number of bone related diseases such as osteosarcoma, malignant hypercalcemia, osteomyelitis. Developing novel drug delivery systems may overcome the adverse reactions caused by traditional administration. This study uses a combination of molecular docking studies and correlation techniques between structure - physical and chemical properties to assess how different bisphosphonates (alendronate, risedronate, pamidronate, zoledronate) interact with polydopamine in order to later design new formulations. The structure of polydopamine is still under discussion therefore, its bisphosphonate binding properties have not been completely established. Polydopamine was modeled by repeated docking of tetrameric subunits combined in two ways which led to simple and mixed oligomers. Fingerprint descriptors, namely electronegativity of the OMO/UMO quantum molecular states, were used for the correlation studies. The correlation coefficients suggest that several atom species such as nitrogen and carbon have increased contributions to the formation of both HOMO and LUMO molecular states. The results showed that the most stable complex was obtained with risedronate for both simple and mixed dopamine oligomers (-186.00 kJ/mol and -184.92 kJ/mol).