Tripfordines A−C, Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii, and Structure Anti-HIV Activity Relationships of Tripterygium Alkaloids

Abstract

Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.

Facile synthesis of hydroxy wilfordic acid, a esterifying unit of anti-HIV sesquiterpene pyridine alkaloids

“…1). Interestingly, as the previous literature, 3 o hydroxy group-containing alkaloids such as wilfortrine showed anti-HIV activity (IC 50 > 100 µg/mL, EC 50 < 0.1 µg/mL, therapeutic index (TI) > 1000), while the similar alkaloids without the hydroxy group such as wilforgine were inactive (IC 50 > 100 µg/mL, EC 50 no suppression) (Duan and Takaishi, 1998;Horiuch et al, 2006). The exciting biological activity of sesquiterpene pyridine alkaloids such as wilfortrine and wilfordine, combined with an effort to elucidate the absolute configuration of the quaternary carbon center, led us to undertake the synthesis of hydroxy wilfordic acid (1).…”

Untargeted analysis of sesquiterpene pyridine alkaloids from the dried roots of Tripterygium wilfordii using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry

“…Sesquiterpene pyridine alkaloids are a large group of highly oxygenated sesquiterpenoids that are predominantly isolated from the plants of the family Celastraceae. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] These alkaloids have attracted attention in various fields of medicine because of their significant biological activities, such as immunosuppressive, [5,15] insect antifeedant, insecticidal, [9,16] anti-HIV, [6,11,12] antitumour [1,2,17] and antiplasmodial. [13] Their potential application requires the development of a method for the reliable, fast, and low-cost analysis of this class of compounds.…”

Natural Sesquiterpenoids

“…286 Several dihydroagarofuran derivatives have been obtained from Austroplenckia populnea, 287 Celastrus angulatus, 288 Celastrus orbiculatus, 289 Celastrus paniculatus, 290 Euonymus nanoides, 291 Microtropis fokienensis, 292 Pleurostylia opposita, 293 Reissantia buchananii 294 and Tripterygium wilfordii. 295 Insights into the molecular mechanism of action of this type of sesquiterpenes, as specific non-transported inhibitors of human P-glycoprotein, have been described. 296 The new eudesmanolides which have been obtained from different species are listed in Table 2.…”