Comparison of 3-carbethoxy-4-phenyl-but-3-en-2-one and methylene quinuclidinone as a ligand to reactivate mutant p53: molecular docking study in three types of crystal structure mutant p53: 2BIM, 2JIY, and 2J21

Abstract

The existence of a large number of mutant p53 in cancer cell nuclei gives a poor prognosis. However, mutant p53 existence creates a challenge to design a new anticancer compound targeted to mutant p53. The 3-carbethoxy-4-phenyl-but-3-en-2-one is a novel compound that was designed as an anticancer agent targeted to mutant p53. Further evaluation of this compound was done by in silico examination employing Auto Dock Vina as molecular docking software. Molecular docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one had lower binding energy than methylene quinuclidinone (MQ). Visual inspection of the docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one docked in the binding pocket crystal structures of mutant p53 (2BIM, 2J1Y, and 2J21), forming a hydrogen bonding or hydrophobic interaction with Cys-124, and the distance between double bonds of α, β-unsaturated of 3-carbethoxy-4-phenyl-but-3-en-2-one with –SH group of Cys-124 were shorter than MQ. These results demonstrated that 3-carbethoxy-4-phenyl-but-3-en-2-one is a promising ligand to mutant p53 in many types of mutations and predicted to have better activity than MQ as a mutant p53 reactivator especially in cancers with mutation type Arg-273-His and Arg-245-Trp.