Otobaphenol

Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells.[Pubmed:34488935]

BMB Rep. 2021 Nov;54(11):563-568.

Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1WT and PDHA13SD were transduced. Since PDHA13SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1WT and PDHA13SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and Otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation. [BMB Reports 2021; 54(11): 563-568].

Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.[Pubmed:21425681]

Nat Prod Commun. 2011 Feb;6(2):231-4.

The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-Otobaphenol (14), was found to be the most selective compound on L. panamensis.

Three new compounds from Kadsura longipedunculata.[Pubmed:18670115]

Chem Pharm Bull (Tokyo). 2008 Aug;56(8):1143-6.

Two new tetrahydrofuran lignans, kadlongirins A and B (1, 2), a new cadinane-type sesquiterpenoid, 2,7-dihydroxy-11,12-dehydrocalamenene (3), together with seven known lignans, grandisin, fragransin B1, vladirol F, kadsuralignan C, Otobaphenol, isoanwulignan, and 4-[4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxy-phenol, were isolated from the leaves and stems of Kadsura longipedunculata. The structures of these new compounds were elucidated by spectroscopic methods. Compound 2 exhibited weak anti-human immunodeficiency virus-1 activity with an EC50 value of 16.0 microg/ml, and therapeutic index (TI) value of 6.7.

Inhibition of protein tyrosine phosphatase 1B by lignans from Myristica fragrans.[Pubmed:16752372]

Phytother Res. 2006 Aug;20(8):680-2.

Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and Otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.

The natural antioxidant otobaphenol delays the permeability transition of mitochondria and induces their aggregation.[Pubmed:12880483]

Antioxid Redox Signal. 2003 Jun;5(3):281-90.

The lignan Otobaphenol, (8R,8'R,7R)-4'-hydroxy-5'-methoxy-3,4-methylenedioxy-2',7,8,8'-neolignan, extracted from Virola Aff. Pavonis leaves, completely inhibits at a concentration of 2.5 micro M the Fe(3+)-ascorbate-induced lipoperoxidation of rat liver mitochondria that was determined by oxygen consumption and accumulation of thiobarbituric acid-reactive species. At 25 micro M, it delays the mitochondrial permeability transition induced by tert-butyl hydroperoxide or Ca(2+), substantially inhibits the state 3 respiration, does not affect the state 4 respiration and the ADP/O ratio (with succinate), diminishes the rate of Ca(2+) uptake by mitochondria, and delays the ruthenium red-insensitive uncoupler-induced release of the loaded Ca(2+). Dose-dependent delaying of the calcium-induced swelling of mitochondria in the presence of Otobaphenol nonlinearly correlates with its 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. At 75 micro M and higher, this lignan causes mitochondrial aggregation and is able to aggregate itself, without mitochondria. The formed aggregates of Otobaphenol do not cause an aggregation of subsequently added mitochondria. Thus, Otobaphenol seems to be a promising target to prevent the oxidative stress death of cells.

XVIII: Eperudiendiol, Glycerides and Neolignans from Fruits of Osteophloeum platyspermum1.[Pubmed:17340250]

Planta Med. 1984 Feb;50(1):53-5.

The fruits of OSTEOPHLOEUM PLATYSPERMUM (Myristicaceae) contain sitosterol, eperu-8(20),13-dien-3alpha,15-diol, glyceryl laurodimyristate, glyceryl 1,3-lauromyristate and five neolignans: dihydroguaiaretic acid, hydroxyotobain, hydroxyoxootobain, guaiacin and Otobaphenol.