Isolation of Diacyl Glycerol Acyl Transferase (DGAT) Inhibitors from Pachydictyon coriaceum

Abstract

The pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) has emerged as a target for the treatment of obesity and type 2 diabetes. Chromatographic analysis of the brown alga, Pachydictyon coriaceum, led to the isolation of diterpene dictyol E and hydroxyisocrenulatin. Pharmacological assay of these compounds demonstrated DGAT inhibitory activity with IC₅₀ values of 46.0 μM and 23.3 μM, respectively.

Diterpenes From the Marine Brown Algae of the Genus Dilophus

“…40 A prenylated-guaiane diterpene, named dictytriene B (35), is obtained from the brown alga D. spiralis collected from Elafonissos Island, Greece. 28 Other Diterpenes of Group I Four prenylated-bicyclogermacrane diterpenes, compounds (36)(37)(38)(39), are separated from the brown alga Dilophus prolificans collected from the New South Wales coast near Sydney, Australia. 41 A prenylated-germacrane diterpene, named dilophol (40), is isolated from the brown alga D. ligulatus collected from the littoral zone of the east coast of Sicily (Porto Palo), Italy.…”

“…29 Compound 32 shows moderate inhibitory activity against rat liver diacyl glycerol acyl transferase with IC 50 values of 46.0 µM. 37 A prenylated-guaiane diterpene, termed dictyoxide (33), is isolated from the brown alga D. ligulatus collected at Aci Castello, Sicily, Italy. 38 Compound 33 is also separated from the alga D. spiralis collected from Elafonissos Island, Greece.…”

Diterpenes from the Marine Algae of the Genus Dictyota

“…(TC5) with EC 50 values of 100, 133, and 92 μM, respectively. Compound 7 also displayed a significant inhibitory effect on rat liver microsomal diacylglycerol acyltransferase with an IC 50 value of 46.0 μM [ 24 ]. Dictyol G acetate ( 8 ) was obtained from D. volubilis , collected from the reef flat of Geoffrey Bay, Magnetic Island, Australia [ 25 ], and also from D. binghamiae , collected from Barkley Sound, British Columbia [ 26 ].…”

Therapeutic Strategies for Metabolic Diseases: Small‐Molecule Diacylglycerol Acyltransferase (DGAT) Inhibitors

“…[56] 2-Arachidonoylglycerol (2-AG) present in the brain is a natural ligand for endocannabinoid receptors, which regulate various physiological events such as appetite. [78,81] In brief, rat livers are rinsed and then homogenized in nine volumes of STE buffer with a Teflon-glass homogenizer. [9] TAGs synthesized by DGATs are then either stored in cytosolic lipid droplets, or, in some organs such as the liver and small intestine, are secreted as components of lipoproteins.…”

“…[77] The method generally used is that developed by Coleman et al for the preparation of microsomes from rat liver. [78,81] In brief, rat livers are rinsed and then homogenized in nine volumes of STE buffer with a Teflon-glass homogenizer. Pellets containing microsomes are re-suspended in STE buffer without EDTA and stored at À70 8C before DGAT activity assay.…”