Magnosalin

Heterogeneous photoredox flow chemistry for the scalable organosynthesis of fine chemicals.[Pubmed:32144271]

Nat Commun. 2020 Mar 6;11(1):1239.

Large-scale photochemical synthesis of high value chemicals under mild conditions is an ideal method of green chemical production. However, a scalable photocatalytic process has been barely reported due to the costly preparation, low stability of photosensitizers and critical reaction conditions required for classical photocatalysts. Here, we report the merging of flow chemistry with heterogeneous photoredox catalysis for the facile production of high value compounds in a continuous flow reactor with visible light at room temperature in air. In the flow reactor system, polymeric carbon nitrides, which are cheap, sustainable and stable heterogeneous photocatalysts, are immobilized onto glass beads and fibers, demonstrating a highly flexible construction possibility for devices of the photocatalytic materials. As an example of the production of high value chemicals, important chemical structures such as cyclobutanes, which are basic building blocks for many pharmaceutical compounds, like Magnosalin, are synthesized in flow with high catalytic efficiency and stability.

Solvent Extraction and Identification of Active Anticariogenic Metabolites in Piper cubeba L. through (1)H-NMR-Based Metabolomics Approach.[Pubmed:30012946]

Molecules. 2018 Jul 16;23(7). pii: molecules23071730.

The aim of this study was to determine the effects of different solvents for extraction, liquid(-)liquid partition, and concentrations of extracts and fractions of Piper cubeba L. on anticariogenic; antibacterial and anti-inflammatory activity against oral bacteria. Furthermore, (1)H-Nuclear Magnetic Resonance (NMR) coupled with multivariate data analysis (MVDA) was applied to discriminate between the extracts and fractions and examine the metabolites that correlate to the bioactivities. All tested bacteria were susceptible to Piper cubeba L. extracts and fractions. Different solvents extraction, liquid(-)liquid partition and concentrations of extracts and fractions have partially influenced the antibacterial activity. MTT assay showed that P. cubeba L. extracts and fractions were not toxic to RAW 264.7 cells at selected concentrations. Anti-inflammatory activity evaluated by nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated cells showed a reduction in NO production in cells treated with P. cubeba L. extracts and fractions, compared to those without treatment. Twelve putative metabolites have been identified, which are (1) cubebin, (2) yatein, (3) hinokinin, (4) dihydrocubebin, (5) dihydroclusin, (6) cubebinin, (7) Magnosalin, (8) p-cymene, (9) piperidine, (10) cubebol, (11) d-germacrene and (12) ledol. Different extraction and liquid(-)liquid partition solvents caused separation in principal component analysis (PCA) models. The partial least squares (PLS) models showed that higher anticariogenic activity was related more to the polar solvents, despite some of the active metabolites also present in the non-polar solvents. Hence, P. cubeba L. extracts and fractions exhibited antibacterial and anti-inflammatory activity and have potential to be developed as the anticariogenic agent.

Synthesis of cyclobutane lignans via an organic single electron oxidant-electron relay system.[Pubmed:24349680]

Chem Sci. 2013 Jun 1;4(6).

A direct method to synthesize lignan cyclobutanes and analogs via photoinduced electron transfer is presented. A variety of oxygenated alkenes are employed to furnish terminal or substituted cyclobutane adducts with complete regiocontrol, yielding cycloadducts with trans stereochemistry. Key to minimizing competing cycloreversion is the inclusion of an aromatic electron relay (ER). This method has been adapted to the synthesis of the natural products Magnosalin and pellucidin A.

Two neolignans from Perilla frutescens and their inhibition of nitric oxide synthase and tumor necrosis factor-alpha expression in murine macrophage cell line RAW 264.7.[Pubmed:11844692]

Bioorg Med Chem Lett. 2002 Feb 25;12(4):649-51.

Two neolignans were isolated from leaves of Perilla frutescens (Labiatae) as inhibitors of nitric oxide syntheses (IC50 5.9 microM and 53.5 microM, respectively) and tumor necrosis factor-alpha in lipopolysaccharide-activated RAW 264.7 cells. Their structures were identified as 1beta,2alpha,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobuta ne (Magnosalin), and 1alpha,2beta,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobuta ne (andamanicin), and their activities were confirmed as resulted from the suppressed expression of inducible nitric oxide synthase enzyme and from the secretion of tumor necrosis factor-alpha from activated macrophages.

Synthesis of a magnosalin derivative, 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine, and the anti-angiogenic and anti-rheumatic effect on mice by oral administration.[Pubmed:11844686]

Bioorg Med Chem Lett. 2002 Feb 25;12(4):623-7.

We describe here the synthesis and the anti-angiogenic and anti-rheumatic activities of 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine (TAS-202), a derivative of Magnosalin, which is a natural product isolated from Flos magnoliae. TAS-202 inhibited the proliferation of vascular endothelial cells more potently than Magnosalin, and when given orally it inhibited basic fibroblast growth factor (bFGF)-induced angiogenesis and collagen-induced arthritis in mice. This Magnosalin derivative with anti-angiogenic effects is a candidate for the treatment of rheumatoid arthritis.

Lignans from Mosla scabra.[Pubmed:11014287]

Phytochemistry. 2000 Aug;54(8):909-12.

Two new cyclobutane-type lignans, named moslolignans A and B, together with two known ones, andamanicin and Magnosalin, were isolated from the whole plant of Mosla scabra. Their structures were established as 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(3- methoxy-4,5-methylene-dioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cycl obutane and 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(2, 5-dimethoxy-3,4-methylenedioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cyclobu tane by spectroscopic methods. This is the first report of naturally-occurring cyclobutane-type lignans with asymmetrical substitutions.

Inhibitory effects of anti-rheumatic drugs containing magnosalin, a compound from 'Shin-i' (Flos magnoliae), on the proliferation of synovial cells in rheumatoid arthritis models.[Pubmed:9716260]

Immunopharmacology. 1998 May;39(2):139-47.

This study was undertaken to examine the effects of Magnosalin, a compound isolated from 'Shin-i' (Flos magnoliae) on proliferation of synovial cells isolated from MRL/1pr and collagen-induced arthritis (CIA) mice, and rheumatoid arthritis (RA) patients. Magnosalin (2.39-23.9 microM) inhibited 5% fetal bovine serum (FBS)-stimulated [3H]-thymidine incorporation into the synovial cells in the MRL/1pr mice. The effect of Magnosalin was greater than that of hydrocortisone, bucillamine and magnoshinin (another compound from 'Shin-i'), but weaker than that of corticosterone. The effects of Magnosalin for FBS-induced thymidine incorporation into the cells of the CIA mice and the RA patients were significantly greater than those in the corresponding control mice and osteoarthritis patients. Interleukin (IL)-1alpha increased the incorporation of thymidine into the synovial cells in the C57BL/6J mice to a greater degree than did basic fibroblast growth factor (bFGF) or platelet-derived growth factor BB-homodimer (PDGF-BB). The inhibitory effect of Magnosalin on the submaximal action of IL-1alpha was significantly greater than that of bFGF, PDGF-BB or FBS. These results offer evidence that Magnosalin suppresses the proliferation of synovial cells in RA models by inhibiting IL-1alpha-stimulated action.

Inhibitory effect of magnosalin derived from Flos magnoliae on tube formation of rat vascular endothelial cells during the angiogenic process.[Pubmed:8913501]

Biol Pharm Bull. 1996 Oct;19(10):1304-6.

An aqueous water extract of Flos magnoliae, a Japanese Sino-medicine, inhibits angiogenesis in adjuvant-induced mouse pouch granuloma. Magnosalin (MSA) and magnoshinin (MSI), neolignans isolated from magnolia, have a crucial role in the anti-angiogenic effect of magnolia (Kimura et al., Int. Arch. Allergy Appl. Immunol., 93, 365 (1990); Phytother. Res., 6, 209 (1992)). We investigated the effects of these neolignans on tube formation of endothelial cells (EC) cultured in type I collagen gel during the angiogenic process. MSA (0.1-10 microM), MSI (0.23-7 microM) and corticosterone (CS: 0.3-30 microM) inhibited fetal bovine serum (FBS)-stimulated tube formation in a concentration-dependent manner. Their 30% inhibitory concentration (IC30, 95% confidence limits) values were 0.51 (0.20-1.27) for MSA, 8.14 (2.48-26.7) for MSI and 3.65 microM (2.47-5.40) for CS, respectively. MSA and MSI (1-3 microM) also inhibited interleukin (IL)-1 alpha-stimulated tube formation in a concentration-dependent manner. Their IC50 values (95% confidence limits) were 1.22 (1.01-1.47) for MSA and 0.74 microM (0.24-2.31) for MSI against a submaximal concentration (69 pM) of IL-1 alpha-stimulated tube formation. Their inhibitory effects on the action of IL-1 alpha were non-competitive. These results demonstrate that MSA inhibited FBS-stimulated tube formation with a greater potency than MSI. The inhibitory effect of MSA on the action of FBS differed from that on the action of IL-1 alpha.

Inhibitory effects of magnoshinin and magnosalin, compounds from "Shin-i" (Flos magnoliae), on the competence and progression phases in proliferation of subcultured rat aortic endothelial cells.[Pubmed:1460807]

Jpn J Pharmacol. 1992 Sep;60(1):59-62.

Anti-proliferative effects of magnoshinin and Magnosalin derived from "Shin-i" (Flos magnoliae) were investigated using subcultured endothelial cells (EC) of rat aorta. The inhibitory effects of magnoshinin were 2-fold greater at 10 micrograms/ml than that of Magnosalin on the increase in cell number when EC were stimulated by 5% fetal bovine serum. In the 3H-thymidine incorporation monitored at 3 hr-intervals, magnoshinin (0.1-3 micrograms/ml) prolonged the starting time of DNA synthesis and reduced the rate of incorporation into EC. Magnosalin (0.3-3 micrograms/ml) reduced only the incorporation rate. These results suggest that magnoshinin inhibits both the competence phase and progression phase, but Magnosalin preferentially inhibits the progression phase in EC proliferation.

Selective inhibition by magnosalin and magnoshinin, compounds from "Shin-i" (Flos magnoliae), of adjuvant-induced angiogenesis and granuloma formation in the mouse pouch.[Pubmed:1712537]

Agents Actions Suppl. 1991;32:197-201.

Inhibitory effects of Magnosalin and magnoshinin, compounds from the crude drug "Shin-i" (Flos magnoliae), on angiogenesis and pouch granuloma formation in mice induced by an adjuvant containing croton oil were investigated. The anti-chronic inflammatory effect of "shin-i" was caused by selective inhibition of angiogenesis by Magnosalin and of granuloma formation by magnoshinin.

Selective inhibition by magnosalin and magnoshinin, compounds from 'shin-i' (Flos magnoliae), of adjuvant-induced angiogenesis and granuloma formation in the mouse pouch.[Pubmed:1713572]

Int Arch Allergy Appl Immunol. 1990;93(4):365-70.

Inhibitory effects of Magnosalin and magnoshinin, compounds from the crude drug 'Shin-i' (Flos magnoliae), on angiogenesis and pouch granuloma formation induced by an adjuvant containing croton oil were investigated. Magnosalin inhibited angiogenesis 2.4-fold (intra-pouch) and 9.7-fold (intraperitoneal) more strongly than granuloma formation. The inhibition of angiogenesis by Magnosalin was 5-fold (intra-pouch) and 21-fold (intraperitoneal) weaker than that by hydrocortisone. In contrast, intraperitoneal magnoshinin inhibited granuloma formation 2.5-fold more strongly than angiogenesis. The regression coefficients of anti-angiogenesis vs. the inhibition of granuloma formation were 1.79 for Magnosalin, 1.11 for hydrocortisone, and 0.61 for magnoshinin. These results show that the anti-chronic inflammatory effect of 'Shin-i' was caused by selective inhibition of angiogenesis by Magnosalin and of granuloma formation by magnoshinin.

Anti-Inflammatory Effect of Neolignans Newly Isolated from the Crude Drug "Shin-i" (Flos Magnoliae).[Pubmed:17340515]

Planta Med. 1985 Aug;51(4):291-3.

The anti-inflammatory effects of the major components of the dried flower buds of MAGNOLIA SALICIFOLIA were determined using the pouch granuloma method in mice. Though alkaloids, fatty acids, essential oils, and lignans had no anti-inflammatory effects, neolignans (magnoshinin and Magnosalin) significantly inhibited the granuloma tissue formation. The inhibitory effect of magnoshinin was particularly strong, being nearly half of that of hydrocortisone acetate when administered orally. Some differences were noted in the mode of action between the neolignans and the steroidal drugs as the neolignans selectively inhibited the granuloma tissue formation but did not affect the exudation of pouch fluid. The structural specificity of neolignans was also found on their anti-inflammatory effect.