Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors

An overview of the chemical constituents from the genus Delphinium reported in the last four decades

“…Several alkaloids possessed at least one uncommon substituent. For example, alkaloids 262, 263 and 264 possess D 1,2 , D 2,3 and D 5,6 groups, [75][76][77] respectively, and alkaloids 256-260 possess an N-C (19) -O-C (1) mixed acetal unit. [78][79][80][81][82] Staphisadrine (267) from D. staphisagria features an aldehyde at C-18, 83 and peregrinine (261) from D. peregrinum var.…”

“…82 Alkaloids 261 and 262 contain a b-oriented OAc group at C-6. 75,82 The other alkaloids mainly vary in the quantity, position and orientation of common oxygenated substituents, including OH, OMe and OAc. Most of the oxygenated substituents are located at C-1, C-6, C-8, C-16, and C-19.…”

“…Most of the oxygenated substituents are located at C-1, C-6, C-8, C-16, and C-19. Alkaloids 269-270 and 266 have a hydroxyl group at C-10, 75,84,85 which is a rare substitution pattern. Generally, aconitine-type DAs have a 16-OMe moiety, but cardiopetaline (290) from D. cardiopetalum and souline (297) from D. souliei are exceptions to this statement, as they lack this denudatum 88 and souline B (318) from D. souliei, 89 both featuring a hexanolactone C ring, were reported.…”

Bioactive Alkaloids from Plants Poisonous to Livestock in North America

“…Methyllycaconitine is also used as a pharmacological tool to block alpha‐7 nAChR. For example, it can block acetylcholine evoked currents in rat fetal hippocampal neurons at picomolar concentrations providing pharmacological evidence that the neuronal depolarization is mediated by alpha‐7 nAChR,, and some norditerpenoid alkaloids isolated from D. denudatum have been reported to act as acetylcholinesterase inhibitors . Structure‐function studies of norditerpenoid alkaloids have shown that the aromatic ester functional group on MLA is a significant haptophore, and that the succinimide group imparts significant toxicity to the alkaloids ,.…”

“…For example, it can block acetylcholine evoked currents in rat fetal hippocampal neurons at picomolar concentrations providing pharmacological evidence that the neuronal depolarization is mediated by alpha-7 nAChR, [18,19] and some norditerpenoid alkaloids isolated from D. denudatum have been reported to act as acetylcholinesterase inhib -1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 itors. [20] Structure-function studies of norditerpenoid alkaloids have shown that the aromatic ester functional group on MLA is a significant haptophore, [21] and that the succinimide group imparts significant toxicity to the alkaloids. [22,23] Current research interest in larkspur alkaloids includes the identification of new alkaloids, [24,25], species alkaloid composition, risk assessment, [26][27][28] and the study of biological activities in rats and insects.…”