Multitarget Anti-Alzheimer Potential of Piperanine and Heraclenol Supported by Cytotoxicity, Antifungal, and In Silico Studies

Abstract

Natural products remain valuable sources of multifunctional therapeutics for complex diseases. In this study, the anti-Alzheimer, anticancer, antimicrobial, and computational properties of Piperanine and Heraclenol were investigated using integrated in vitro and in silico approaches. Heraclenol exhibited potent inhibition of Alzheimer's disease-related enzymes, with IC50 values of 1.42 +/- 0.14 & micro;M (AChE), 0.98 +/- 0.05 & micro;M (MAO-A), and 14.93 +/- 1.95 & micro;M (MAO-B), outperforming reference inhibitors in several assays. Piperanine also showed notable enzyme inhibition and demonstrated superior antibacterial activity against Escherichia coli (MIC = 11.07 +/- 0.78 & micro;g mL(-1)). In cytotoxicity studies, Heraclenol displayed remarkable activity against colon cancer cells, particularly CL40 (IC50 = 1.07 +/- 0.02 & micro;M), whereas Piperanine showed moderate to strong effects across multiple cancer cell lines. Molecular docking, MM/GBSA calculations, and 100 ns molecular dynamics simulations confirmed favorable binding affinities and stable interactions with the target enzymes. Overall, the findings identify Heraclenol and Piperanine as promising multifunctional natural scaffolds for the development of novel therapeutic agents against Alzheimer's disease and cancer.