Bioassay-guided isolation of terpenoids from the soft coral and assessment of their antidiabetic and cytotoxic activities.

This study represents the first report on the secondary metabolites from the soft coral . Nine terpenoids (1-9) were isolated by antidiabetic-guided isolation, including a new xeniaphyllane-type diterpenoid (Sclerohumin O, 1) and a new norcaryophyllene-type sesquiterpenoid (Norsclerohumin P, 6). These compounds feature a distinctive 4/9-fused ring system, which was the first isolated in the genus. All compounds were subjected to evaluation for their antidiabetic and cytotoxic activities. Notably, compound 1 demonstrated substantial inhibitory activity against key metabolic enzymes implicated in diabetes, namely α-amylase, α-glucosidase, and lipase, with IC values of 100.3 ± 1.02, 170.0 ± 0.92, and 16.1 ± 2.15 μM, respectively. Moreover, compound 1 demonstrated potent cytotoxicity against pancreatic cancer cell lines, with IC values of 11.01 ± 1.43 μM (MIA PaCa-2), 19.06 ± 0.28 μM (Panc-1), and 17.86 ± 0.87 μM (KPC). Additionally, compounds 3 and 4 showed strong inhibitory activity against the MIA PaCa-2 cell line, with IC values of 2.52 ± 0.27 μM and 2.54 ± 0.38 μM, respectively. Enzyme kinetics, molecular docking, and molecular dynamics simulations were also performed to further elucidate the experimental findings. These results underscore the potential of marine-derived terpenoids as promising multifunctional bioactive agents with therapeutic applications in the management of diabetes, obesity, and pancreatic cancer.