A New Diterpene with Cytotoxic Potential Against Human Tumor Cells

Cancer is one of the most feared diseases in the world. Its incidence has increased steadily in recent years; it represents a significant burden of disease and is among the leading causes of death globally. Consequently, the search for novel compounds that serve as potential candidates for pharmacotherapeutic options and that can be used as treatments or adjuvants to control this disease is urgent. In this context, plant-derived phenolic diterpenes have shown antitumor activity against several types of cancer, inhibiting DNA synthesis, lipid metabolism, and bioenergetics of these cells, among other mechanisms, making these compounds an excellent alternative to continue investigating. The objective of this research was to evaluate the action of the previously undescribed natural diterpene 3,3'-diisopropyl-2,2',5,5'-tetramethoxy-6,6'-dimethylbiphenyl-4,4'-diol (biisoespintanolcompound 2), against several human tumor cell lines (A549, MDA-MB-231, DU145, A2780, A2780-cis) and the non-tumor cell line MRC-5. Experiments with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescence with propidium iodide (PI), 4',6-diamidino-2-phenylindole dilactate (DAPI), and green plasma revealed the cytotoxicity of 2 against these cells. Furthermore, morphological and chromogenic studies demonstrated the action of 2 on cell morphology and its inhibitory capacity of reproductive viability for colony formation in A549 cells. Furthermore, 3D experiments validated the damage caused by this diterpene in these cells. These results contribute to the search for novel compounds with antitumor potential and serve as a basis for advancing studies into the mechanisms of action of these compounds and the development of synthetic derivatives or analogs with a better antitumor profile.