A new (+)-curcuphenol derivative from the Indonesian marine sponge <i>Myrmekioderma</i> sp.: dual cytotoxic apoptotic and antiviral activities against A549, HeLa, and DENV-2

The Indonesian marine biodiversity holds huge potential for drug discovery, particularly from marine sponges, which serve as a rich source of cytotoxic agents. In this study, the sponge <i>Myrmekioderma</i> sp., collected from Bitung, North Sulawesi, Indonesia, was investigated. Bioassay-guided isolation led to the identification of two sesquiterpene compounds: the known (+)-curcuphenol (<b>1</b>) and a new derivative, dihydrocurcuphenol (<b>2</b>). Both compounds exhibited potent cytotoxic activity against A549 human lung cancer cells (IC₅₀ of 31.52 and 37.60 μg/mL, respectively) and HeLa cervical cancer cells (IC₅₀ of 30.83 and 50.27 μg/mL, respectively). The cytotoxic effects of these compounds were linked to apoptosis, as confirmed by positive annexin V and PI staining observed under a fluorescence microscope, as well as molecular docking studies. Additionally, compounds <b>1</b> and <b>2</b> elicited significant antiviral activity against DENV-2 with EC₅₀ values of 17.89 and 12.59 μg/mL, respectively.