Computational Analysis of Selected Phytochemicals for their PARP Inhibitory Potential in Cancer

Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising agents in cancer prevention due to their ability to target the DNA repair machinery of cancerous cells. PARP enzymes repair single-strand DNA breaks through the base excision repair pathway. In cancer cells, particularly those with deficiencies in homologous recombination, PARP aids in DNA repair pathways and promotes cancer cell survival. PARP inhibitors suppress the enzyme function, thus inducing apoptosis in cancerous cells. Phytochemicals, bioactive compounds derived from plants, have gained increasing attention for their potential role in cancer prevention and treatment. We have investigated selected phytochemicals such as cinnamaldehyde, baicalein, curcumin, galangin, ellagic acid, resveratrol, pinocembrin, genistein, quercetin, and apigenin against PARP. The assessment of selected phytochemicals, including baicalein, galangin, ellagic acid, genistein, and apigenin, reveals promising attributes through various computational analyses. Specifically, these compounds exhibit favorable docking scores, indicating strong binding affinity to their target molecules. Molecular dynamic simulations for 10 nanoseconds were performed to validate the findings. Moreover, their potential as PARP inhibitors suggests a plausible role in inhibiting DNA repair mechanisms, an essential aspect of cancer therapy. These compounds were found to exert PARP inhibition through direct interference with enzymatic activity or modulation of PARP expression. This targeted investigation underscores the potential of these phytochemicals as PARP inhibitors, contributing to the advancement of precision cancer therapeutics.