Discovery of novel coffee diterpenoids with inhibitions on Cav3.1 low voltage-gated Ca2+ channel
2022
Seven new (1–4, 6–8) diterpenoids with rare skeletons and seven known ones (9, 12, 17, 18 and 23–25) were isolated from roasted beans of Coffea arabica L. Together with previously obtained diterpenoids, a total of 26 molecules (1–25, 4a) were evaluated their activities on Caᵥ3.1 low voltage-gated Ca²⁺ channel. Compounds 1, 3, 6, 7, 12, 13, 17, 19 and 24 exhibited noticeable Caᵥ3.1 inhibitions (41.2%-96.1%) at 10 μM. The IC₅₀ values of 1, 6, 7, 12, 13, 17 and 24 are 2.9, 2.3, 0.68, 14.8, 11.6, 6.1 and 6.8 μM, respectively. The ring moiety at C-18 and C-19, and esterification of OH-17 with long-chain fatty acids seem important for their activities. Further studies indicated that 1 and cafestol may act on different binding sits with the Caᵥ3.1 blocker Z944, which is in clinical trial. Significantly, the present study initially shows that coffee diterpenoids are potential natural resources for Caᵥ3.1 inhibitors.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by National Agricultural Library