Microwave-assisted synthesis, characterization, and molecular docking studies of new chlorophthalazine derivatives as anticancer activity

A series of phthalazine derivatives have been synthesized using green protocol methods under microwave irradiation. This involved subjecting chlorophthalazine to microwave irradiation and employing various reagents, including hydrazine derivatives, primary and secondary amines, and active methylene, to generate the novel phthalazine derivatives. Subsequently, a comparison was made between the yield percentage and reaction time of the resulting products obtained from conventional methods and those obtained through microwave irradiation. The structures of all new compounds were confirmed by physical properties and spectral analysis. The phthalazine compounds demonstrated significant anticancer activity against three cancer cell lines and showed promising selectivity when compared with doxorubicin. Compound 6 exhibited the best anticancer activity, with IC₅₀ 1.739 µM, 0.384 µM, and 1.52 µM against MCF7, HCT116, and HepG2 cell lines, respectively. The docking results confirmed that the drugs exert their activity by inhibiting PARP-1. The binding scores were in accordance with the experimental IC₅₀, with compound 6 exhibiting the best binding score and retaining the essential binding interactions with the active site. The results of our computational research have revealed that our phthalazine compounds possess a unique structure that effectively inhibits PARP-1.