Alkaloids of Delphinium grandiflorum and their implication to H2O2-induced cardiomyocytes injury. (1st May 2021)

• Record Type: Journal Article
• Authors: Wang, Yali; Sun, Dejuan; Chen, Yanmei; Xu, Jinyu; Xu, Yang; Yue, Xinyi; Jia, Jingming; Li, Hua; Chen, Lixia
• Is Part Of: Bioorganic & medicinal chemistry. Volume 37(2021)
• Publication Date: 2021-05-01
• Subjects: C19-diterpenoid alkaloid -- Delphinium grandiflorum -- Grandiflodines (B-12) -- Oxidative stress -- Antioxidant activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116113
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Three new diterpenoid alkaloids (1 –3 ), and eight known alkaloids (4 –11 ) were isolated from the aerial parts of Delphinium grandiflorum . Grandifline A (1 ) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7 N C17 hemiaminal moiety and a lactone fragment through the linkage of C-17 O C19 unit. And we named this newly-discovered class of rearranged C19 -diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2 ) is the first naturally-occurring 7, 17-secolycoctonine diterpenoid alkaloid with a C-7 O C17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1 –11 on H2 O2 -induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC50 values of 1.881 ± 0.680 μM and 1.904 ± 0.750 μM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H2 O2 -induced H9C2 cells.