Chemical Constituents of Anneslea fragrans and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line

Abstract

An ethanolic extract of Anneslea f ragrans leaves showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition, with a PC 50 value of 9.6 μg/mL. Phytochemical investigation of this active extract led to the isolation of two new secondary metabolites, fragranones A (1) and B (2), along with 15 previously reported compounds. The structure elucidation of the new compounds was achieved by HRFABMS, acid hydrolysis, NMR, and ECD spectroscopic analysis. Fragranone A (1) is the first example of a rare natural product bearing an acetonide glucose moiety. Fragranone B ( 2) is representative of a rare class of natural products with a threonolactone unit linked to a chalcone through an ether linkage. The isolated compounds exhibited antiausterity activity against PANC-1 cells under nutrient-deprived conditions, and betulin ( 14) was found to be the most potent compound tested, with a PC 50 value of 8.4 μM. In addition, fragranone A (1) was found to suppress PANC-1 cancer cell migration in real time.

Activity Guided Isolation of Phenolic Compositions from Anneslea fragrans Wall. and Their Cytoprotective Effect against Hydrogen Peroxide Induced Oxidative Stress in HepG2 Cells

“…2′,3,4,4′-Tetrahydroxydihydrochalcone ( 5 ) possessed the molecular formula as C 15 H 14 O 5 and separated (15 mg) as white powder. 1 H NMR (400 MHz, DMSO- d 6 ) and ESI-MS ( m / z 275 [M + H] + ) data were consistent with that reported in the literature [ 26 ]. The identification was further supported by 13 C NMR (125 MHz, DMSO- d 6 ): δ 203.9 (s, C=O), 164.7 (s, C-2′), 164.2 (s, C-4′), 144.9 (s, C-3), 143.3 (s, C-4), 133.0 (d, C-6′), 131.8 (s, C-1), 118.9 (d, C-6), 115.7 (d, C-2), 115.4 (d, C-5), 112.5 (s, C-1′), 108.2 (d, C-5′), 102.4 (d, C-3′), 39.5 (t, C- α ), 29.2 (t, C- β ).…”

“…Most of the polyphenols, especially flavonoids and phenolic acids, are exploited into popular antioxidant foods (nutraceuticals) and present a series of human benefits [ 17 ]. In our previous study, the A. fragrans leaves have been proven to be a good resource of polyphenols [ 26 ]. However, the antioxidant activity of the extract from A. fragrans leaves and its phytochemicals have not been investigated yet.…”

“…In this way, the bioactivity-guided fractionation of BF-C to E led to the isolation of seven individual phenolic compounds. Their structures were identified as confusoside ( 1 ) [ 34 ], vacciniifolin ( 2 ) [ 34 ], 1-[4-(β- d -glucopyranosyloxy)-2-hydroxyphenyl]-3-(4-hydroxy-3-methoxyphenyl)-1-propanone ( 3 ) [ 35 ], ( S )-naringenin-7- O - β - d -glucopyranoside ( 4 ) [ 22 ], 2′,3,4,4′-tetrahydroxydihydrochalcone ( 5 ) [ 26 ], (epi)-catechin ( 6 ) [ 26 ], and cornoside ( 7 ) [ 36 ] ( Figure 1 B) by the analysis of 1D-NMR and ESI-MS data and comparison with the previously reported compounds in the literature. Among them, compounds 3 , 4 , and 7 were isolated from this plant for the first time.…”

A Triterpene Lactone from Callistemon citrinus Inhibits the PANC‐1 Human Pancreatic Cancer Cells Viability through Suppression of Unfolded Protein Response

“…It also inhibited Akt phosphorylation. [6,23] During our search for antiausterity agents, [6][7][8][9] we found that 3β-hydroxy-13,28-epoxyurs-11-en-28-one (ursenolide; Figure 1), isolated from an active dichloromethane extract of Callistemon citrinus (CURTIS) SKEELS leaf from Egypt, inhibited PANC-1 human pancreatic cancer cells viability preferentially in nutrient-deprived medium (NDM) with a PC 50 value of 0.4 μM, while no cytotoxicity was observed in Dulbecco's modified Eagle's medium (DMEM). [24] Therefore, we investigated the effect of the ursenolide on PANC-1 human pancreatic cancer cell morphology, migration, colony formation, and the underlying mechanism with particular focus on its effect on the unfolded protein response markers (GRP78 and GRP94) and Akt/mTOR pathway.…”

“…PC 50 describes the concentration at which 50 % of the tumor cells were killed preferentially in nutrients‐deprived medium (NDM) while showing no cytotoxicity in normal medium (DMEM). Several plants‐derived antiausterity agents with selective cytotoxicity against PANC‐1 human pancreatic cancer cells under nutrient‐deprived conditions have been reported [6–9] . Interestingly, some of these agents could also inhibit PANC‐1 human pancreatic cancer cell migration and colony formation under nutrient‐rich conditions.…”