Caesalsins A-N, structurally diverse cassane diterpenoids from the seeds of Caesalpinia sinensis and their inhibitory effects on α-glucosidase and anti-inflammatory activities.

Abstract

Fourteen previously undescribed cassane diterpenoids, named caesalsins A-N (1-14), along with ten known related compounds (15-24), were isolated from the seeds of Caesalpinia sinensis. Their structures and absolute configurations were determined through comprehensive spectral analysis, single-crystal X-ray diffraction, NMR computational techniques, and electronic circular dichroism calculations. Notably, compound 1 represents an unprecedented 8,14-secocassane diterpenoid featuring an unreported carbon skeleton, while compound 2 is the first naturally occurring 11,12-secocassane diterpenoid. Compounds 3 and 4 are uncommon rearranged cassane diterpenoids characterized by a 6/6/5/5 spirocyclic ring system. Compounds 19-22 exhibited potent inhibitory activity against α-glucosidase, with IC50 values ranging from 9.02 ± 1.30 to 44.64 ± 0.91 μM; notably, compound 21 demonstrated remarkable inhibition with an IC50 value of 9.02 ± 1.30 μM. Additionally, compounds 6, 11, 17, and 21 displayed moderate inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells, with IC50 values between 15.74 ± 0.27 and 36.14 ± 1.01 μM, among which 17 exerted superior anti-inflammatory potency. Molecular docking studies of 19-22 were conducted to clarify their interactions with α-glucosidase. Furthermore, plausible biosynthetic pathways for 1-4 were proposed. These findings expand the chemical diversity of cassane diterpenoids and provide promising bioactive compounds for the development of potential anti-diabetic and anti-inflammatory agents.