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

Abstract

This study represents the first report on the secondary metabolites from the soft coral Sclerophytum humesi. 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 Sclerophytum 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 IC₅₀ 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 IC₅₀ 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 IC₅₀ 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.