67560-68-3Relevant academic research and scientific papers
A LIGNAN FROM ACTINODAPHNE LONGIFOLIA
Tanaka, Hitoshi,Nakamura, Takeshi,Ichino, Kazuhiko,Ito, Kazuo
, p. 952 - 954 (1989)
A new lignan, actifolin, was isolated from the leaves of Actinodaphne longifolia and the structure was established on the basis of chemical and spectroscopic evidence.Key Word Index - Actinodaphne longifolia; Lauraceae; lignan; actifolin; piperitol.
Characterization of a structural leoligin analog as farnesoid X receptor agonist and modulator of cholesterol transport
Atanasov, Atanas G.,Dirsch, Verena M.,Hiebl, Verena,Ladurner, Angela,Linder, Thomas,Mihovilovic, Marko D.,Schnürch, Michael,Schuster, Daniela,Wang, Limei
, p. 1097 - 1107 (2020)
The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 μM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/β, and peroxisome proliferator-activated receptors β/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.
Design and synthesis of a compound library exploiting 5-methoxyleoligin as potential cholesterol efflux promoter
Linder, Thomas,Geyrhofer, Sophie,Papaplioura, Eleni,Wang, Limei,Atanasov, Atanas G.,Stuppner, Hermann,Dirsch, Verena M.,Schnürch, Michael,Mihovilovic, Marko D.
, (2020/02/18)
5-Methoxyleoligin and leoligin are natural occurring lignans derived from Edelweiss (Leontopodium nivale ssp. alpinum), displaying potent pro-angiogenic and pro-arteriogenic activity. Cholesterol efflux from macrophages is associated with reverse cholesterol transport which inhibits the development of cardiovascular disease. Within this study, we developed a modular and stereoselective total synthesis of 5-methoxyleoligin which can be readily used to prepare a novel compound library of related analogs. The target 5-methoxyleoligin was synthesized exploiting a recently disclosed modular route, which allows also rapid synthesis of analogous compounds. All obtained products were tested towards macrophage cholesterol efflux enhancement and the performance was compared to the parent compound leoligin. It was found that variation on the aryl moiety in 2-position of the furan ring allows optimization of the activity profile, whereas the ester-functionality does not tolerate significant alterations.
Leoligin-inspired synthetic lignans with selectivity for cell-type and bioactivity relevant for cardiovascular disease
Linder, Thomas,Liu, Rongxia,Atanasov, Atanas G.,Li, Yuanfang,Geyrhofer, Sophie,Schwaiger, Stefan,Stuppner, Hermann,Schnürch, Michael,Dirsch, Verena M.,Mihovilovic, Marko D.
, p. 5815 - 5820 (2019/06/17)
Recently, a natural compound leoligin, a furan-type lignan, was discovered as an interesting hit compound with an anti-inflammatory pharmacological activity profile. We developed a modular and stereoselective approach for the synthesis of the edelweiss-de
PHARMACEUTICAL COMPOSITIONS COMPRISING LIGNANS AND THEIR DERIVATIVES FOR TREATING HYPERPLASTIC DISEASES
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Page/Page column 48, (2016/11/07)
The present invention relates to a pharmaceutical composition comprising specific compounds which may be obtained from Leontopodium alpinum Cass. (Edelweiss). A preferred compound is leoligin (=(2S,3R,4R)-4-(3,4-dimethoxybenzyl) -2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl(2Z)-2-methylbut-2-enoat]). Corresponding means and methods in respect of medical uses of the compounds are described. The present invention also provides a medical device comprising, containing or having been contacted with the compound. The compounds provided herein may particularly be used in the treatment of hyperplastic diseases, in particular intimal hyperplasia, e.g. stenosis, restenosis, atherosclerosis and the like. Also envisaged herein is the use of these compounds in the treatment of proliferative diseases, such as leukemia, prostate cancer and lung cancer.
Furanoid and furofuranoid lignans from Daphne oleoides
Riaz, Muhammad,Ullah, Nisar,Mehmood, Arshad,Nawaz, Hafiz Rab,Malik, Abdul,Afza, Nighat
, p. 1216 - 1220 (2007/10/03)
Furofuranoid lignan (1) and (2) and furanoid lignan (3) have been isolated from Daphne oleoides and their structures elucidated through chemical and spectroscopic studies as 2-(3′-methoxy-4′-O-α-D-galactopyranosylphenyl)-6-(3″- methoxy-4″-hydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (1), 2-(3′,5′-dimethoxy-4′-O-α-D-galactopyranosylphenyl)-6- (3″-methoxy-4″-hydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (2), and 4,9′-dihydroxy-3,3′-dimethoxy-4′-O-ss-D-glucopyranosyl- 7′,9-epoxylignan (3). Two known lignans (4) and (5) have also been reported for the first time from this species.
