Evaluating the Anticancer Properties of Novel Piscidinol A Derivatives: Insights from DFT, Molecular Docking, and Molecular Dynamics Studies

Cancer is characterized by uncontrolled cell growth and spreading throughout the body. This study employed computational approaches to investigate 18 naturally derived anticancer piscidinol A derivatives (<b>1</b>-<b>18</b>) as potential therapeutics. By examining their interactions with 15 essential target proteins (HIF-1α, RanGAP, FOXM1, PARP2, HER2, ERα, NGF, FAS, GRP78, PRDX2, SCF complex, EGFR, Bcl-xL, ERG, and HSP70) and comparing them with established drugs such as camptothecin, docetaxel, etoposide, irinotecan, paclitaxel, and teniposide, compound <b>10</b> emerged as noteworthy. In molecular dynamics simulations, the protein with the strongest binding to the crucial 1A52 protein exceeded druglikeness criteria and displayed extraordinary stability within the enzyme's pocket over varied temperatures (300-320 K). Additionally, density functional theory was used to calculate dipole moments and molecular orbital characteristics, as well as analyze the thermodynamic stability of the putative anticancer derivatives. This finding reveals a well-defined, potentially therapeutic relationship supported by theoretical analysis, which is in good agreement with subsequent assessments of their potential <i>in vitro</i> cytotoxic effects of piscidinol A derivatives (<b>6</b>-<b>18</b>) against various cancer cell lines. Future <i>in vivo</i> and clinical studies are required to validate these findings further. Compound <b>10</b> thus emerges as an intriguing contender in the fight against cancer.