QSAR studies of phthalazinones: novel inhibitors of poly (ADP-ribose) polymerase

Over activation of poly (ADP-ribose) polymerase has been involved in the pathogenesis of several diseases including stroke, myocardial infarction, diabetes, shock, neurodegenerative disorder, allergy, and several other inflammatory processes. Owing to the dual response of PARP-1 to DNA damage and its involvement in cell death, pharmacological modulation of PARP-1 activity may constitute a useful tool to increase the activity of DNA-binding antitumor drugs. Quantitative structure activity relationship (QSAR) study vis-à-vis physico-chemical parameters and forward feed neural network analysis for a series of phthalazinone derivatives as potent inhibitors of poly (ADP-ribose) polymerase was performed. The result of QSAR studies obtained allows us to recognize such physico-chemical parameters of phthalazinone derivatives which can be strictly related to the PARP-1 inhibitory activity.