Antiangiogenic Tocotrienol Derivatives from Garcinia amplexicaulis

Abstract

Phytochemical investigation of a dichloromethane extract from Garcinia amplexicaulis stem bark led to the isolation of four new tocotrienols (1-4); two known tocotrienols, two triterpenes, and a xanthone were also isolated. Their structures were mainly established using NMR and MS methods. The main compounds isolated, δ-amplexichromanol (1) and γ-amplexichromanol (2), were evaluated on VEGF-induced angiogenesis using a Matrigel assay. Compounds 1 and 2 inhibited in vitro angiogenesis of VEGF-induced human primary endothelial cells in the low nanomolar range. Their capacity to inhibit VEGF-induced proliferation of endothelial cells partially explained this activity, although δ-amplexichromanol (1) also prevented adhesion and migration processes.

Natural 6-hydroxy-chromanols and -chromenols: structural diversity, biosynthetic pathways and health implications

“…[37][38][39][40][41][42] It has been detected in different amounts within the Clusiaceae family including Tovomitopsis psychotriifolia, Clusia obdeltifolia, Clusia burlemarxii, Clusia pernambucensis, Garcinia kola and together with g-garcinoic acid (31) in the bark of Garcinia amplexicaulis. 43,44 Recently, g-garcinoic acid was isolated in small amounts from the Algerian conifer Cedrus atlantica (Pinaceae). 45 A mixture of 2(Z)-d-garcinoic acid and 2(E)-d-garcinoic acid was isolated from the stem of Clusia obdeltifolia.…”

Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine‐Substituted δ‐Tocotrienol Derivative

“…To address these questions, the proposed C−F bond hydrolysis products, M1 and M2 , of DT3‐F2 ( 1 ) in mouse liver microsomes were synthesized (See supporting information for the synthesis). Interestingly, M2 , also known as δ‐amplexichromanol, is a natural product present in the stem bark of Garcinia amplexicaulis , a shrug found in New Caledonia . To the best of our knowledge, the synthesis of this natural product has never been reported.…”

“…Reaction progress was monitored by TLC (silica-coated glass plates) and visualized after p-anisaldehyde stain solution (recipe: 135 mL alcohol + 5 mL H 2 SO 4 + 3.7 mL p-anisaldehyde + 1.5 mL glacial acetic acid) staining, or by GC-MS (Agilent, 5975 series system) or TLC-MS (Advion). NMR spectra were recorded in CDCl 3 at 400 MHz for 1 H, 100 MHz for 13 C NMR, and 600 MHz for 19 F NMR. Chemical shifts δ are given in ppm using tetramethylsilane as an internal standard.…”

“…Interestingly, M2, also known as δ-amplexichromanol, is a natural product present in the stem bark of Garcinia amplexicaulis, a shrug found in New Caledonia. [19,20] To the best of our knowledge, the synthesis of this natural product has never been reported. Normal phase chromatography and fluorescence detection (λ excitation = 292 nm, λ emission = 330 nm) was used for better separation of Z/E isomers and improved detection limits.…”

A Brief Journey of Tocotrienols as Anticancer Agents

“…Few studies were conducted to improve their in vivo activity by making semi synthetic derivatives which had shown promising results in mice model of breast cancer [41][42][43]. In a recent published article, tocotrienol was targeted by using targeted vesicles [44].…”