α,β-Pipitzols and α,β-Isopipitzols from Natural Quinone Perezone: Quantum Chemistry, Docking, Chemoinformatic, and Pharmacological Studies.

PARP-1 and COX-2 have played important roles in several carcinomas, representing potential therapeutic targets; natural products have constituted interesting alternatives in cancer research, and complementary computational methods are relevant tools for the proposal of new molecules. Therefore, in this work, a theoretical study of a set of four derivatives of perezone and isoperezone, i.e., α-pipitzol, β-pipitzol, α-isopipitzol, and β-isopipitzol, employing quantum chemistry, bioinformatics, and docking, was performed. Conformational studies were accomplished to obtain minimum energy structures. Subsequently, they were optimized by the B3LYP hybrid method and the 6-311++G(d,p) basis set. With this same level of theory, the geometrical, electronic, and spectroscopic properties and the reactivity parameters were determined; moreover, a molecular docking evaluation was performed to determine their activity towards COX-2 and PARP-1. Additionally, a cytotoxicity activity assay was performed against various cancer cell lines; thus, α-pipitzol and β-pipitzol showed the greatest affinity for COX-2, and the α-isopipitzol exhibited two relevant interactions. Regarding α-pipitzol, it exhibited both affinity and an important interaction with PARP-1. Regarding β-pipitzol, it displayed the lowest inhibitory concentration in A549 (64.49 µM); nevertheless, α-isopipitzol presented the lowest inhibitory concentrations, 83.59 µM and 87.85 µM for U37 and MCF-7 cell lines, respectively.