Sorbaria kirilowii (Regel) Maxim.由来のククルビタン型トリテルペンとそのPDE1阻害活性

Sorbariakirine A (1), a cucurbitane-type triterpene, along with nine known compounds (2-10), were isolated from the aerial parts (stems and leaves) of Sorbaria kirilowii (Regel) Maxim. The structure of compound 1 was determined through comprehensive spectroscopic analysis (IR, MS, 1D/2D NMR, and CD). Compound 4 showed potent phosphodiesterase 1 inhibitory effect (IC₅₀ = 12.90 ± 0.12 µg/mL). Enzyme kinetics demonstrated that compound 4 irreversibly inhibits PDE1. Molecular docking studies reveal that 4 adopts a binding mode that forms a 'covalent-anchored synergistic non-covalent interaction network' with the PDE1 protein, thereby enhancing its inhibitory activity. Additionally, In Silico drug-likeness predictions using the pkCSM platform were performed to evaluate the drug-likeness of these compounds.