Antioxidant and cytotoxic isoprenylated coumarins from Mammea americana

Antioxidant-guided fractionation of Mammea americana L. seeds resulted in the identification of three new isoprenylated coumarins, mammea B/BA hydroxycyclo F (1), mammea E/BC (2), and mammea E/BD (3). In addition, twelve known isoprenylated coumarins, mammea A/AA (4), mammea A/AA cyclo D (5), mammea A/AA cyclo F (6), mammea A/AC cyclo D (7), mammea A/AD cyclo D (8), mammea B/BA (9), mammea B/BA cyclo F (10), mammea B/BB (11), mammea B/BC (12), mammea B/BD (13), mammea E/BA (14), and mammea E/BB (15), as well as two known flavanols, (+)-catechin (16) and (-)-epicatechin (17) were identified. The fifteen isoprenylated coumarins were screened for their cytotoxicity in the SW-480, HT-29, and HCT-116 human colon cancer cell lines and antioxidant capacities in the DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical assay. Compounds 1 - 15 exhibited significant cytotoxic activities in the SW-480, HT-29, and HCT-116 human colon cancer cell lines (IC50 ranges 13.9 - 88.1, 11.2 - 85.3, and 10.7 - 76.7 microM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 microM), a drug frequently used for human colon cancer treatment. Compounds 2 - 4, 9, and 11 - 15 displayed high antioxidant activity in the DPPH assay (IC50 range 86 - 135 microM), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 microg/mL) in the DPPH assay. The results of these assays were used to study the structure-activity relationships for this class of compounds. In the SW-480 cell line, the three new coumarins, 1 - 3, also exhibited dose-dependent increases in sub-diploid cells by flow cytometry, indicating that they induce apoptosis.     

沙田柚皮中的香豆素类成分

目的:研究沙田柚(Citrus grandis Osbeck.)果皮的化学成分.方法:利用多种色谱层析方法进行分离纯化,根据理化性质和波谱数据对分离得到的化合物进行结构鉴定.结果:从新鲜沙田柚皮的95%乙醇提取物中分离得到10个香豆素类化合物,分别鉴定为8-(3-hydroxy-2-methoxy-3-methylbutyl)-7-methoxy coumarin(1)、mexoticin(2)、环氧橙皮油素(3)、meranzin(4)、meranzin hydrate (5)、isomeranzin(6)、异前胡素(7)、橙皮油素(8)、蛇床子素(9)和伞形花内酯(10).结论:化合物1～4为首次从该植物中分离得到.     

Neuroprotective coumarins from the root of<Emphasis Type="Italic">Angelica gigas</Emphasis>: Structure-activity relationships

An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae) exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Using neuroprotective activity-guided fractionation, nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-beta-D-glucopyranoside (3), (S)-peucedanol-7-O-beta-D-glucopyranoside (4), (S)-peucedanol-3'-O-beta-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7), isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3, exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from 0.1 to 10 microM. To explore the structure-activity relationships of coumarins, sixteen previously isolated compounds; 10-25, were simultaneously evaluated in the same system. Our results revealed that cyclization of the isoprenyl group, such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of coumarin, as well as lipophilicity played an important role in the neuroprotective activity of coumarins.     

Inhibitory activity of monoamine oxidase by coumarins fromPeucedanum japonicum

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.     

九里香化学成分的研究

自广东产芸香科(Rutaceae)植物九里香(Murraya paniculata(L.)Jack.)叶中分离得到六个香豆精,其中三个化合物为新的香豆精,根据光谱(UV,IR,NMR和MS)分析和化学方法确定九里香甲素(isomexoticin)九里香乙素(murpanidin)和九里香丙素(murpanicin)分别为(一)5,7-二甲氧基-8-(2′,3′-二羟基-3′-甲基丁基)香豆精(Ⅰ),(+)7-甲氧基-8-(1′,2′-二羟基-3′-甲基-3′-丁烯基香豆精(Ⅲ)和7-甲氧基-8-(1′-乙氧基-2′-羟基-3′-甲基-3′-丁烯基)香豆精(Ⅳ)。同时也得到三个已知香豆精murragatin(Ⅱ),murralongin(Ⅴ)和5,7-二甲氧基-8-(3′-甲基-2′-酮基丁基)香豆精(Ⅵ),最后一个是首次自本植物中得到的。     

Coumarins from Coriaria nepalensis

Two new coumarins (1) and (2), along with seven known coumarins 3-9, were isolated from the leaves and stems of Coriaria nepalensis Wall. The two new compounds were established as 7-hydroxy-6-methoxy-3,8-bis(3-methyl-2-butenyl) coumarin (1) and 7-hydroxy-6-methoxy-3-(3-methyl-2-butenyl) coumarin (2), on the basis of 1D and 2D NMR techniques. The known compounds 3, 6-9 were isolated from this plant for the first time.     

A new coumarin from the stem of<Emphasis Type="Italic">Angelica dahurica</Emphasis>

One new and three known coumarins were isolated from the CHCl3 soluble fraction of Angelica dahurica stem. On the basis of spectral data, the structures of the isolated compounds were determined to be scopoletin, angelol I, angelol H and 6-[(1S), 2(R)-2, 3-dihydroxy-1-methoxy-3-methylbutyl]-7-methoxycoumarin; the latter being isolated for the first time from a plant source.     

Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation

Since glycation can lead to the onset of diabetic complications due to chronic hyperglycemia, several indigenous Artemisia species were evaluated as potential inhibitors of advanced glycation endproducts (AGE). Among them, the Artemisia capillaris plant demonstrated the highest AGE inhibitory activity. Repeated column chromatography was performed to isolate a new acylated flavonoid glycoside, acacetin-7-O-(6″-O-acetyl)-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, along with 11 known flavonoids (acacetin-7-O-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, linarin, quercetin, hyperoside, isorhamnetin, isorhamnetin 3-galactoside, isorhamnetin 3-glucoside, isorhamnetin 3-arabinoside, isorhamnetin 3-robinobioside, arcapillin, and cirsilineol), six coumarins (umbelliferone, esculetin, scopoletin, scopolin, isoscopolin, and scoparone), and two phenolic derivatives (4,5-di-O-caffeoylquinic acid and chlorogenic acid). In determining the structure-activity relationship (SAR), it was found that the presence and position of hydroxyl group of test coumarins (coumarin, esculin, isoscopoletin, daphnetin, 4-methylcoumarin, and six isolated coumarins) may play a crucial role in AGE inhibition. A free hydroxyl group at C-7 and a glucosyl group instead of a methoxyl group at C-6 are two important parameters for the inhibitory potential of coumarins on AGE formation. A. capillaris and five key AGE inhibitors, including 4,5-di-Ocaffeoylquinic acid, umbelliferone, esculetin, esculin, and scopoletin, were identified as potential candidates for use as therapeutic or preventive agents for diabetic complications and oxidative stress-related diseases. We understand this to be the first detailed study on the SAR of coumarins in AGE inhibition.     

Two new coumarins from Murraya paniculata

Two new coumarins, murrmeranzin (1) and murralonginal (2), together with four known compounds minumicrolin (3), murrangatin (4), meranzin hydrate (5) and hainanmurpanin (6) have been isolated from the aerial parts of Murraya paniculata. The structures of these compounds were determined through spectral analysis. Minumicrolin (3) showed mild butyrylcholinesterase inhibition activity.     

Studies on coumarins of a chinese drug "Qian-Hu"

Three new and four known coumarins were isolated from a Chinese drug "Zi-Hua Quian-Hu" (Shikazenko in Japanese), the root of PEUCEDANUM DECURSIVUM M AXIM. (Umbelliferae). The new compounds were proved to be 3'(S)-senecioyloxy-4'(R)-hydroxy-3',4'-dihydroxanthyletin, 3' (S)-hydroxy-4' (R)-senecioyloxy-3',4'-dihydroxanthyletin and 3'(S)-angeloyloxy-4'(R)-acetoxy-3',4'-dihydroxanthyletin. The known coumarins were identified to be decursidin, bergapten, nodakenetin and nodakenin, respectively.     

Antibacterial and anticoagulant activities of coumarins isolated from the flowers of Magydaris tomentosa

The phytochemical investigation of the acetone and methanol extracts of the flowers of Magydaris tomentosa (Desf.) DC afforded six known coumarins as well as (+)-meranzin hydrate (7), not previously reported as a natural product. The antibacterial activity of umbelliprenin (1), osthol (2), imperatorin (3), citropten (4) and (+)-meranzin hydrate (7) was tested against Gram-positive and Gram-negative bacteria. All coumarins (1-7) isolated in this study inhibited growth of all bacterial strains tested (MIC between 16 and 256 microg/mL), the most active being imperatorin (3) (MICs between 32 and 128 microg/mL) and citropten (4) (MICs between 16 and 256 microg/mL). The anticoagulant activity of compounds 1-4 and 7 was also evaluated.     

Chemical constituents from the aerial parts of Waltheria indica Linn.

A phytochemical investigation on the aerial parts of Waltheria indica Linn. led to the isolation of 16 compounds,including five terpenoids (1–5), four coumarins (6–9), six flavonoids (10–15), and one phenylpropanoid glycoside (16). The structuresof these compounds were identified by spectroscopic data analysis and comparison with those reported in the literatures. Except for12 and 15, all the compounds were isolated from W. indica for the first time. Moreover, coumarins were firstly reported to be obtained from this herb. The NO production inhibitory activities of all the isolated compounds in LPS-induced BV-2 cells were also presented.     

Studies on the chemical constituents of Rutaceae++ plants. LXVI. The chemical constituents of Toddalia asiatica (L.) Lam. (T. aculeata Pers.). (1). Chemical constituents of the root bark]

Chemical constituents of the root bark of Toddalia asiatica (L.) Lam. (T. aculeata Pers.), Rutaceae, were examined. In addition to twelve known coumarins [toddaculin (2), coumurrayin (5), toddanone (6), 8-(3,3-dimethylallyl)-6,7-dimethoxycoumarin (7), isopimpinellin (8), 6-(3-chloro-2-hydroxy-3-methylbutyl)-5,7-dimethoxycoumarin (9), 6-formyllimettin (10), 5,7,8-trimethoxycoumarin (12), toddasin (13), (+)-toddanol (14), 6-(2-hydroxy-3-methoxy-3-methylbutyl)-5,7-dimethoxycoumarin (18), and toddalolactone (21)] five new coumarins [toddalenol (17), toddalosin (19), 5-methoxysuberenon (23), toddalenone (24), and 8-formyllimettin (25)] were isolated. Furthermore seven known benzo[c]phenanthridine alkaloids [des-N-methylchelerythrine (4), oxychelerythrine (15), arnottianamide (16), oxyavicine (22), avicine (30), chelerythrine (31), and chelerythrine-psi-cyanide (34)] and four known quinoline alkaloids [N-methylflindersine (11), 4-methoxy-1-methyl-2-quinolone (20), skimmianine (35), integriquinolone (36)], one known triterpenoid [beta-amyrin (3)], and four unknown components [unknown I-IV (26)-(29)] were isolated.     

2D NMR spectroscopic analyses of archangelicin from the seeds of Angelica archangelica

A total of six coumarins, bergapten (1), xanthotoxin (2), imperatorin (3), isoimperatorin (4), phellopterin (5) and archangelicin (6), have been isolated from an n-hexane extract of the seeds of Angelica archangelica. The results of comprehensive 2D NMR analyses of archangelicin are discussed.     

Chemical constituents of the root ofDystaenia takeshimana and their anti-inflammatory activity

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with beta-sitosterol (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)-marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.     

Apoptosis inducing activity of 4-substituted coumarins from Calophyllum brasiliense in human leukaemia HL-60 cells

With the objective of identifying anti-tumour-promoting agents, we carried out a primary screening of ten 4-substituted coumarins isolated from Calophyllum brasiliense Camb. (Guttiferae), to determine the ability of these compounds to inhibit proliferation of the human leukaemia cell line HL-60. Among the 4-substituted coumarins isolated, calophyllolide (2) and mammea B/BB (3) showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin increased in a time-dependent manner after treatment with calophyllolide (2) or mammea B/BB (3). In addition, the activity of caspase-9 and caspase-3 was also enhanced in a time-dependent manner upon treatment with the 4-substituted coumarins 2 and 3. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by 4-substituted coumarins 2 and 3. These results suggest that calophyllolide (2) and mammea B/ BB (3) induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.     

Isolation And Structure Elucidation Of 5,7-disubstituted Simple Coumarins In The Fruits Of Heracleum Mantegazzianum

In addition to bergapten ( 1 ), xanthotoxin ( 2 ), isopimpinellin ( 3 ), imperatorin ( 4 ), and pimpinellin ( 5 ), for the first time 5,7-disubstituted simple coumarins, limettin (5,7-dimethoxycoumarin) ( 6 ) and a new compound 5-methoxy-7-(3,3-dimethylalliloxy)-coumarin ( 7 ), have been isolated from the fruits of Heracleum mantegazzianum Somm. et Lev. The new compound 7 is a derivative of anisocoumarin B. The structures of 6 and 7 were determined on the basis of 1D and 2D NMR spectra.     

Isolation And Structure Elucidation Of 5,7–disubstituted Simple Coumarins In The Fruits Of Heracleum Mantegazzianum

In addition to bergapten ( 1 ), xanthotoxin ( 2 ), isopimpinellin ( 3 ), imperatorin ( 4 ), and pimpinellin ( 5 ), for the first time 5,7-disubstituted simple coumarins, limettin (5,7-dimethoxycoumarin) ( 6 ) and a new compound 5-methoxy-7-(3,3-dimethylalliloxy)-coumarin ( 7 ), have been isolated from the fruits of Heracleum mantegazzianum Somm. et Lev. The new compound 7 is a derivative of anisocoumarin B. The structures of 6 and 7 were determined on the basis of 1D and 2D NMR spectra.     

Bioactive coumarins from the leaves of Murraya omphalocarpa

Using antiplatelet aggregation as a guide to fractionation, eight coumarins, omphalocarpinol (1), 5,7-dimethoxy-8-(3'-methyl-2'-oxobutyl)coumarin (2), murralongin, murrayanone, omphamurin (5), murragleinin, mexoticin, and murrangatin, were isolated from the leaves of Murraya omphalocarpa. Compound 1 is new, and 5 is a new enantiomer of omphamurin. The structures of these compounds were elucidated on the basis of spectroscopic techniques, and the structure of compound 1 was confirmed by X-ray crystallographic analysis. Among them, compounds 1, 2 and 5 exhibited significant antiplatelet aggregation activity.