Synthesis, Anticancer Activity and Molecular Docking Studies of Pyrazole Conjugated Pthalazine-2-carbonitriles

The pyrazolo conjugated phthalazine derivatives were synthesized with 85-88% yield by the one-pot reaction of diethyl phthalate with hydrazine hydrate, 1H -pyrazole-5-carbaldehydes and malononitrile or ethyl 2-cyanoacetate in [BMIM][OH] as green reaction medium at 70-75 degrees C for 30-45 min. The potential of the synthesized compounds to inhibit cancer growth in HepG2 and MDA-MD-231 cells was evaluated. 3-Amino-1-(1-methyl-1H-pyrazol-5-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile demonstrated remarkable cytotoxicity with IC50 values of 8.2 and 8.7 mu M against MCF-7 and DU145, respectively. Moreover, in silico studies revealed that this compound had a favorable binding energy of -7.1 kcal/mol in inhibiting the human protein mono-ADP-ribosyltransferase PARP15.