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Marmesin, an important coumarin isolated from Broussonetia kazinoki, has been proposed to possess many pharmacological activities including anti-tumor activity. However, the anti-cancer effect of marmesin on esophageal cancer (EC) has not been characterized. The study aimed to explore the anti-cancer role of marmesin using EC cell lines in vitro. Cell proliferation was evaluated by CCK-8 and Edu cell proliferation assays and apoptosis was detected by TUNEL assay. Western blot analysis was used to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, phosphatidylinositol 3-kinase (PI3K), phosphoryrated-PI3K (p-PI3K), protein kinase B (Akt), and phosphoryrated-Akt (p-Akt). The mechanism of action of marmesin was analyzed using network pharmacology approach. Marmesin exhibited anti-proliferative effect against EC cells, which was further confirmed by the reduced expression of Ki67 and PCNA. Marmesin exerted pro-apoptotic activity on EC cells by downregulating Bcl-2 and upregulating Bax. According to the results from network pharmacology approach, we speculated that PI3K/Akt pathway may participate in the effect of marmesin on EC cells. Additionally, the PI3K/Akt pathway was suppressed by marmesin in EC cells. Moreover, forced expression of Akt reversed the inhibition of cell proliferation and induction of apoptosis induced by marmesin in EC cells. Marmesin exerted anti-cancer activity in EC cells by inhibiting the PI3K/Akt pathway.

A simple and efficient approach has been developed for the preparation of coumarin natural products such as dihydroxanthyletin, xanthyletin, decursinol and marmesin starting from commercially avail...

C20H24O10, orthorhombic, P212121 (no. 19), a = 6.3728(6) Å, b = 14.3835(14) Å, c = 20.453(2) Å, V = 1874.8(3) Å3, Z = 4, R gt(F) = 0.0272, wR ref(F 2) = 0.0558, T = 296(2) K.

Chromatographic examination of tissue from suspension cultures of A. visnaga proved their ability to biosynthesis of furanochromone-visnagin and furanocoumarin-marmesin. The occurrence of these two compounds depends on the composition of medium which also influences culture growth and embryogenesis, after subculture for at least l year

Leukemia is one of the highly lethal cancers among all pediatric cancers. With limited drug options and the severe side effects associated with the current chemotherapy, there is pressing need to look for new and novel anticancer agents. Against this backdrop, in the present study we evaluated the anticancer activity of a natural coumarin, marmesin against human leukemia cell line U937 and normal human monocytes It was observed that marmesin exhibited an IC50 value of 40 µM and exerted its cytotoxic effects in a dose-dependent manner. However, the cytotoxic effects of marmesin were comparatively lower for the normal human monocytes as evident from the IC50 of 125 µM. Our results indicated that marmesin inhibits colony formation and induces apoptosis dose-dependently. We also investigated the effect of marmesin on the expression of Bax and Bcl-2 proteins. It was observed that marmesin treatment triggered upregulation of Bax and downregulation of Bcl-2 causing significant increase in the Bax/Bcl-2 ratio, marmesin could also induce ROS mediated alterations in mitochondrial membrane potential. Additionally, marmesin induced G2/M cell cycle arrest and significantly inhibited cell migration potential of leukemia cells at the IC50. Remarkably, marmesin prevent tumor growth significantly in vivo at the dosage of 30 mg/kg in vivo. These results strongly indicate that marmesin may prove to be a novel anticancer lead for the management of leukemia.

In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. Collectively, these findings demonstrate the pharmacological roles and molecular targets of marmesin in regulating NSCLC cell responses and tumor angiogenesis.

Feronia limonia Linn. (Rutaceae) have gained traditional therapeutic importance owing to their high essential oil and coumarins content. Marmesin, a furanocoumarin was identified by TLC and isolated by column chromatography and further purified by Preparative TLC. Presently, there is no appropriate TLC based method available for standardization of F. limonia. A simple, sensitive and accurate high performance thin layer chromatographic (HPTLC) method has been developed for the estimation of marmesin in the methanolic extract of stem bark of Feronia limonia. HPTLC was performed on precoated silica gel 60F254 aluminium plates (20 cm × 20 cm) with Chloroform: Methanol (9.5:0.5), as mobile phase. Quantitative evaluation of the plate was performed in the absorption-reflection mode at 338 nm. The calibration curve was linear in the concentration range of 20 – 100 ng spot–1. The method was validated for precision, repeatability and accuracy. The technique has been applied, for the first time, for the estimation of marmesin. The proposed method was found to be robust, precise, and accurate, it therefore holds potential for detection, monitoring and quantification of marmesin in Feronia limonia and its related formulation.

In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo. These anti-angiogenic activities of marmesin were mediated through inactivation of VEGF-A-stimulated signaling pathways, and down-regulation of cell surface signaling molecules including VEGF receptor-2, human epidermal growth factor receptor-2, integrin β1 and integrin-liked kinase. Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

In parsley (Petroselinum crispum (Mill.) Mansf.) with no decay prior to storage, the incidence rose to 12% after 1 month of storage at 1°C, and the concentration of +marmesin in leaves decreased from 32 to 4 μg g–1 fresh mass (FM). During that time, the concentration of psoralens increased from 8 to 41 μg g–1 FM. When parsley was treated with GA3 prior to storage, incidence of decay following 1 month of storage at 1°C was 3%, and the concentration of +marmesin was 21 μg g–1 FM. Concentrations of psoralens (psoralen, bergapten, and xanthotoxin) during that time reached 15 μg g–1 FM. Bioassays showed that +marmesin has much greater antifungal activity in vitro than psoralens.

The study tested two parsley (Petroslinum crispum) cultivars, ‘Janet’ (resident) and ‘Hazera’ (susceptible), that differ in their response to the fungus Botrytis cinera Pers. During the 4 days after inoculation with B. cinerea, at 24 °C, concentrations of (+)marmesin in leaves sampled from ‘Janet’ and ‘Hazera’ increased from 17 to 145 μg g−1 fresh weight (FW) and from 8 to 25 μg g−1 FW, respectively. After the 4th day, levels decreased. Incidence of decay (necrotic areas) in ‘Janet’ and ‘Hazera’ leaves 4 days post-inoculation with B. cinerea, at 24 °C, were 4 and 68 mm2, respectively. EC50 values of (+) marmesin for the pathogenic fungi B. cinerea, Alternaria alternata (Fr.) Keissler and Sclerotinia sclerotiorum (Lib) De Bray in vitro were found to be 30, 40 and 25 μg ml−1, respectively. (+)Marmesin levels were highly correlated with resistance.

We used solvent extractions, SiO2 column chromatographies, and HPLC to isolate from the bark of Thanakha (Hesperethusa crenulata L) an active crystalline compound for absorbing UV-A radiation (320 to 380 nm). Analyses of low-and high-resolution FAB-MS revealed a compound, named marmesin, with a formula of C14H14O4 and a molecular mass of 246. To determine its chemical structure, we conducted 300 MMz NMR analyses using various probes,1H,13C, and DEPT13C. Our NMR data showed a structure of 2,3-dihydro-2(1 -hydroxy-1 -methylethyl)-furanocoumarin. This active compound contains UV-absorbing chromophores, an aromatic ring, a double bond at C3-C4, and a carbonyl at C2. Its λmax is 335 nm, indicating that marmesin could be commercially useful as a natural UV-A-filtering product

We show evidences that(+)marmesin, rather than linear furanocoumarins (psoralens), may play the major role in celery resistance to pathogens during storage. (+)Marmesin, the precursor of psoralens in celery, has at least 100 times greater antifungal activity in vitro in the dark than psoralens. Increased susceptibility of celery to pathogens during I mo of storage was accompanied by a decrease in (+)marmesin concentration and a corresponding increase in psoralen concentration. An increase in celery decay was negatively correlated with (+)marmesin concentration and positively correlated with psoralen concentration. After 1 mo of storage at 0 or 2 C, the concentration of psoralens increased from 10 to 136 or 78 μg g -1 fr. wt., respectively, while the concentration of (+)marmesin under the same storage conditions decreased from 33 to 4 or II μg g -1 fr. wt., respectively. Incidence of decay after I mo of storage at 0 or 2 C was 62 or 27%, respectively.

Microsomal fractions isolated from parsley cell suspension cultures, which had been challenged with an elicitor from either Alternaria carthami or Phytophthora megasperma f. sp. glycinea, catalyzed the formation of psoralen from synthetic [3-14C](+)marmesin. Whereas psoralen was the only product formed in incubations with Alternaria-induced microsomes, another unidentified product was isolated from incubations with Phytophthora-induced microsomes. The latter product is neither a precursor nor a product of psoralen. In contrast, microsomes isolated from non-induced parsley cells lacked both of these catalytic activities. The formation of psoralen depends on NADPH as a cofactor and molecular oxygen. Blue-light-reversible CO inhibition and inhibition by various synthetic chemicals known to bind to cytochromes P450 indicated that the reaction is catalyzed by an elicitor-inducible cytochrome P450-dependent psoralen synthase. Fractionation of microsomal preparations by centrifugation revealed that psoralen synthase is associated with the endoplasmic reticulum. Our results suggest that the endoplasmic reticulum of cultured parsley cells is the primary target in the previously reported differential induction by elicitors from these two non-pathogenic strains of fungi.

Biosynthetic pathways leading to the furanocoumarins, in contrast with those to simple coumarins, are not well understood. To date, no intermediate in a proposed reaction sequence has been identified. The report presents observations strongly indicating participation of two alpha-hydroxyisopropyldihydrofuranocoumarins, marmesin, and columbianetin as natural intermediates in the elaboration of linear and angular furanocoumarins, respectively. (Author)

The title compounds, natural coumarins or their racemic modifications, were synthesized via malonic acid condensations with appropriate salicylaldehydes. Oxidation of 2,4-dihydroxy-5-(3-methyl-2 butenyl)benzaldehyde with DDQ, peracid, and acid–peracid gave the aldehydes for xanthyletin, marmesin, and decursinol, respectively. Some 14C-labelled coumarins were prepared similarly. The n.m.r. spectral data for the products are presented.

The unit cell parameters of this compound were determined by least-squares calculations from the adjusted angular setting of 25 general reflections. The crystals are monoclinic with the following crystallographic data: a = 5.718(1), b = 13.794(4), c = 7.861(1) A, β = 100.53(2)°, Z = 2 and Dx = 1.34 g · cm−3. The space group according to the systematic absences is P21. The structure of this compound was solved by direct methods and refined by full matrix least-squares with anisotropic temperature factors to R = 0.04. The refined atomic positions indicate a considerable strain within the molecule. The structure is built up from molecules connected by H-atoms forming infinite chains along b-axis.

New coumarins, arnocoumarin (1) and arnottiacoumarin (2), were isolated from X. arnottianum MAXIM. The structures of these coumarins were established by chemical transformation from marmesin (7) and rutaretin methyl ether (10) respectively.

— Marmesin was isolated from the medicinal plant, Afraegle paniculata. Its cytotoxicity and mutagenicity in Chinese hamster V79 cells when sensitized to near ultraviolet (NUV) and long wavelength ultraviolet light or black light (BL) were assayed. Marmesin was extremely cytotoxic in the dark. This cytotoxicity was photoenhanced in NUV and BL; the photoenhanced lethality being higher in NUV than in BL. The LD50 of marmesin under NUV and BL photosensitization were 0.002 μM and (0.012 μM), respectively. In the absence of NUV and BL, marmesin's LD50 was 0.013 μM. NUV and BL without marmesin were not significantly cytotoxic at the fluence rates of 0.29 W/m2 and 4.2 W/m2, respectively, for up to 20 min. In contrast to the observed high cytotoxicity of marmesin, its mutagenicity at the HGPRT locus (AzGr) was weak. The implication of this result in the high incidence of skin cancer in Nigeria in which A. paniculata is used as a medicinal plant is discussed.

Suspension cultures of Ammi majus L. cells produce various linear furanocoumarins in response to treatment with elicitor preparations from either Alternaria carthami Chowdhury or Phytophthora megasperma f.sp. glycinea. Microsomes which were isolated from these cells 14 h after addition of the elicitor efficiently catalyzed the conversion of demethyl [3-14C]suberosin into labelled (+)marmesin in the presence of NADPH and oxygen. In contrast to the chemical cyclization of demethylsuberosin by m-chloroperoxybenzoic acid, the reaction catalyzed by the marmesin synthase proceeded rapidly and no intermediate demethylsuberosin epoxide could be recovered. Significant blue-light-reversible inhibition by carbon monoxide and inhibition by various chemicals known to inhibit reactions dependent on cytochrome P450 suggested that the marmesin synthase is a cytochrome-P450-dependent monooxygenase. Upon prolonged incubation, a subsequent major labelled product originated from (+)marmesin, which was identified as psoralen. The psoralen synthase was also characterized as a cytochrome-P450-dependent monooxygenase. Both the marmesin synthase and the psoralen synthase, as well as enzymes catalyzing the formation of demethylsuberosin and O-prenylumbelliferone from umbelliferone and dimethylallyl diphosphate, were associated with the endoplasmic reticulum in Ammi majus cells and their activities were concomitantly induced by elicitor treatment of the cells. We propose that in vivo these enzymes are active in the lumen of the endoplasmic reticulum from where the furanocoumarin phytoalexins are excreted into the cell culture fluid.

Marmesin has been identified by chromatography and ultraviolet absorption spectrum in extracts of Ruta graveolens, in confirmation of earlier conclusions from tracer experiments that it is an intermediate in furanocoumarin biosynthesis in this species. Trapping experiments with [2-14C]umbelliferone and (+)- or (−)-marmesin were inconclusive, but indicated that only the (+)-form is metabolically active in R. graveolens. This was confirmed in Ruta and also in Heracleum lanatum and Angelica archangelica by direct comparison feedings of [3-14C](+)- and (−)-marmesin. The (+)-isomer was an efficient furanocoumarin precursor, as before, while little if any utilization of (−)-marmesin could be demonstrated.

Furanocoumarins are phytoalexins often cited as an example to illustrate the arms race between plants and herbivorous insects. They are distributed in a limited number of phylogenetically distant plant lineages, but synthesized through a similar pathway, which raised the question of a unique or multiple emergence in higher plants. The furanocoumarin pathway was investigated in the fig tree (Ficus carica, Moraceae). Transcriptomic and metabolomic approaches led to the identification of CYP76F112, a cytochrome P450 catalyzing an original reaction. CYP76F112 emergence was inquired using phylogenetics combined with in silico modelling and site-directed mutagenesis. CYP76F112 was found to convert demethylsuberosin into marmesin with a very high affinity. This atypical cyclisation reaction represents a key step within the polyphenol biosynthesis pathway. CYP76F112 evolutionary patterns suggests that the marmesin synthase activity appeared recently in the Moraceae family, through a lineage-specific expansion and diversification. The characterization of CYP76F112 as the first known marmesin synthase opens new prospects for the use of the furanocoumarin pathway. It also supports the multiple acquisition of furanocoumarin in angiosperms by convergent evolution, and opens new perspectives regarding the ability of cytochromes P450 to evolve new functions related to plant adaptation to their environment.

This work describes the valorization of two natural bioactive coumarins via the semi-synthesis of new derivatives and the study of their antibacterial and anticholinesterase potentials. Marmesin 1 and Scopoletin 2 were isolated from the dichloromethane extract of Ferula lutea (Poir.) Maire roots. Esterification of 1 with a series of acid chlorides, led to the formation of esters 1′a-j. The O-propargylated intermediate 3 was used as dipolarophile affording via 1,3-dipolar cycloaddition the isoxazole-linked coumarins 3′a-f. The study of the antibacterial activity of all the prepared compounds showed that S. aureus and E. faecalis are sensitive towards the ester 1′c and the isoxazole 3′c (MIC = 62.0 µg/mL). Compound 3′b displayed the highest antibacterial effect against all the tested strains (MIC = 62.0 µg/mL). The ester 1′j exhibited the highest anticholinesterase effect (IC50 = 98.0 µg/mL). The drug likeness scores was calculated using Molinspiration software and discussed.

Ferulago trachycarpa (Apiaceae) is a plant used traditionally for its sedative, digestive, carminative and aphrodisiac properties with distribution in West, Southwest and South Anatolian part of Turkey. In this study the antimicrobial activities of fractionally n-hexane, dichloromethane, methanol and only methanol extracts from rhizomes of F. trachycarpa were screened against Stapylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 14153, Enterococcus feacalis ATCC 29212 bacterial strains and fungal strains such as Candida albicans ATCC 10231, C. tropicalis ATCC 750 and C. parapsilosis ATCC 22019 by microdilution method. All extracts have been shown to possess antimicrobial activities against bacteria and fungal strains and according to the antimicrobial results, the isolation of the active constituents was made from the most active n-hexane and dichloromethane extracts. So, four pure compounds are known as coumarin derivatives, crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) as dihydrofuranocoumarin derivative and ulopterol [6- (2’, 3’-dihydroxy-3’-methylbutyl)-7-methoxy-coumarin] were isolated. Crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) which are pure compounds demonstrated antifungal activity with 625 mg/L MIC against C. albicans and antibacterial activity with 1250 mg/L MIC against S. aureus (MRSA). These results indicate that extracts and pure compounds obtained from Ferulago trachycarpa could be a potential for pharmaceutical products which have antimicrobial activity.

The application of preparative thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl (PTLC-DPPH) bioautography technique successfully isolated a lignan sesamin (1), two prenylated coumarins (2 and 3) and a marmesin glycosides (4) from Micromelum minutum methanol bark extract. Compounds 2 and 3 were identified as new compounds whereas 1 and 4 were first isolated from Micromelum genus. Structural identification of all compounds were done by detailed spectroscopic analyses and comparison with literature data. Antioxidant capacities of extract, active fraction and compounds were measured based on DPPH free radical savenging activity, oxygen radical absorbance capacity (ORAC) and β-carotene bleaching. The DPPH activity of methanol extract and its fraction present the IC50 values of 54.3 and 168.9 µg/mL meanwhile the β-carotene bleaching results were 55.19% and 5.75% respectively. The ORAC measurements of M. minutum extract, compounds 2 and 4 showed potent antioxidant activity with the values of 5123, 5539 and 4031 µmol TE/g respectively.

In this study, potential bioactive compounds in the products of the solid fermentation of the paper mulberry tree bark (Broussonetia papyrifera) with a white rot fungus (Perenniporia tephropora) we...

Melicope glabra (Blume) T. G. Hartley from the Rutaceae family is one of the richest sources of plant secondary metabolites, including coumarins and flavanoids. This study investigates the free radical scavenging and antibacterial activities of M. glabra and its isolated compounds. M. glabra ethyl acetate and methanol extracts were prepared using the cold maceration technique. The isolation of compounds was performed with column chromatography. The free radical scavenging activity of the extracts and isolated compounds were evaluated based on their oxygen radical absorbance capacity (ORAC) activities. The extracts and compounds were also subjected to antibacterial evaluation using bio-autographic and minimal inhibitory concentration (MIC) techniques against two oral pathogens, Enterococcus faecalis and Streptococcus mutans. Isolation of phytoconstituents from ethyl acetate extract successfully yielded quercetin 3, 5, 3’-trimethyl ether (1) and kumatakenin (2), while the isolation of the methanol extract resulted in scoparone (3), 6, 7, 8-trimethoxycoumarin (4), marmesin (5), glabranin (6), umbelliferone (7), scopoletin (8), and sesamin (9). The study is the first to isolate compound (1) from Rutaceae plants, and also the first to report the isolation of compounds (2–5) from M. glabra. The ORAC evaluation showed that the methanol extract is stronger than the ethyl acetate extract, while umbelliferone (7) exhibited the highest ORAC value of 24 965 μmolTE/g followed by glabranin (6), sesamin (9) and scopoletin (8). Ethyl acetate extract showed stronger antibacterial activity towards E. faecalis and S. mutans than the methanol extract with MIC values of 4166.7 ± 1443.4 μg/ml and 8303.3 ± 360.8 μg/ml respectively. Ethyl acetate extract inhibited E. faecalis growth, as shown by the lowest optical density value of 0.046 at a concentration of 5.0 mg/mL with a percentage inhibition of 95%. Among the isolated compounds tested, umbelliferone (7) and sesamin (9) exhibited promising antibacterial activity against S. mutans with both exhibiting MIC values of 208.3 ± 90.6 μg/ml. Findings from this study suggests M. glabra as a natural source of potent antioxidant and antibacterial agents.

Phytochemical investigation of the stem barks of Ficus exasperata Vahl. (Moraceae) led to the isolation of two new cinnamic acid derivatives stereoisomers, named ficusanolide A (1) and ficusanolide B (2) along with twelve known compounds: ficusanol (3), umbelliferone-6-carboxylic acid (4), oxypeucedanin hydrate (5), marmesin (6), decursinol (7), beta-amyrin acetate (8), lupeol (9), betulinic acid (10), ursolic acid (11), a mixture of stigmasterol (12) and beta-sitosterol (13), sitosteryl-3-O-beta-D-glucopyranoside (14); and one hemisynthetic derivative : per acetylated betulinic acid (15). Their structures were established by the means of their physical data (melting point, rotatory power), their spectroscopic data, particularly IR, NMR (1H, 13C, DEPT, COSY, HSQC and HMBC) data, and HR-ESIMS data. Crude extract, compounds 1, 2, 3, 5, 6, 7, 9, 10, 11, as well as the semisynthetic derivative 15 were evaluated for their cytotoxic activity on the human cervix carcinoma cell line KB-3-1 and the human colon cancer cell line HT-29. Ursolic acid 11 showed a moderate activity on both cancer cells tested with IC50s of 50.9 mu M and 34.4 mu M respectively.

© 2021 Phytochemical Society of EuropeSeventeen natural coumarin derivatives; badrakemin (1), 14′-acetoxybadrakemin (2), badrakemone (3), 14′-acetoxybadrakemone (4), colladonin (5), colladonin acetate (6), 14′-acetoxycolladonin (7), karatavicinol (8), deltoin (9), smyrnioridin (10), marmesin (11), osthol (12), oxypeucedanin (13), oxypeucedanin hydrate (14), isoimperatorin (15), scopoletin (16), and umbelliprenin (17), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer's disease as well as tyrosinase (TYR) as the target for Parkinson's disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates.

A study of the chemical constituents obtained from twigs of Melicope lunu-ankenda (Gaertn.) T.G. Hartley (Rutaceae) led to the isolation and structure elucidation of two new coumarins, 7-(4-hydroxy-3-methylbutanoxy) coumarin and 7-(3-methyl-4-carboxybutanoxy) coumarin methyl ester, named melilunumarin A ( 1 ) and melilunumarin B ( 2 ), respectively. A new benzaldehyde derivative, 3,4-dihydro-3,4-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-carboxaldehyde, named melilunumane ( 6 ), was also isolated and characterized, as well as five previously reported compounds, 6-deoxyhaplopinol ( 3 ), marmesin ( 4 ), umbelliferone ( 5 ), kokusaginine ( 7 ) and evolitrin ( 8 ). Among the five isolated coumarins, melilunumarin A ( 1 ), 6-deoxyhaplopinol ( 3 ) and marmesin ( 4 ) exhibited significant inhibitory activity towards Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.

Highlights • Extracts of less polarity from B. rubescens displayed significant antifungal activity. • Two coumarins (xanthyletin and 7-demethylsuberosin) were isolated from antifungal extracts of B. rubescens. • A chromatographic method to detect and quantify both coumarins is described. • Xanthyletin and 7-demethylsuberosin exhibited in vivo and in vitro strong antifungal activity. • 7-Demethylsuberosin was metabolized slowly by C. gloeosporioides to marmesin and decursinol., Anthracnose, caused by the fungus Colletotrichum gloeosporioides (Penz.) Penz. & Sacc., is the most limiting fungal disease of mango and papaya crops in Colombia. The in vivo and in vitro activity against C. gloeosporioides of the extracts from sawdust of Brosimum rubescens Taub. (Moraceae) was evaluated. The extracts of less polarity (n-hexane and dichloromethane) displayed the greatest inhibitory effects. Then, the coumarins xanthyletin (2.74 % d.w.) and 7-demethylsuberosin (2.19 % d.w.) were isolated from these extracts. The compound 7-demethylsuberosin displayed a strong in vivo and in vitro antifungal activity. Furthermore, the metabolism of 7-demethylsuberosin by the fungus C. gloeosporioides was analyzed. The fungus slowly detoxified 7-demethylsuberosin to marmesin and decursinol. Therefore, the high antifungal activity and low level of detoxification make 7-demethylsuberosin, and the extracts that contain it, promising candidates for controlling C. gloeosporioides. Sawdust of B. rubescens may be considered a valuable source of extracts and coumarins with antifungal activity.

Psoralen synthase and angelicin synthase responsible for the formation of psoralen and angelicin in Peucedanum praeruptorum Dunn were identified and functionally characterized, respectively. Furanocoumarins were reported to possess several activities such as anticancer, anti-inflammatory and neuroprotective, and function as phytotoxin and allelochemical in plants. Furanocoumarins are the main bioactive ingredient in P. praeruptorum which is a commonly used traditional Chinese medicine. Phenylalanine ammonia lyase (PAL), 4-coumarate: CoA ligase (4CL), p-coumaroyl CoA 2’-hyfroxylase (C2’H) were cloned previously to elucidate the biosynthetic mechanism of coumarin lactone ring. However, the genes involved in complex coumarins in P. praeruptorum have not been explored. Herein, putative psoralen synthase CYP71AJ49 and angelicin synthase CYP71AJ51 were cloned from P. praeruptorum. In vivo and in vitro yeast assays were conducted to confirm their activities. Furthermore, the results of High Performance Liquid Chromatography–Electrospray Ionization Mass Spectrometry (HPLC–ESI–MS) verified that CYP71AJ49 catalyzed the conversion of marmesin to psoralen, and CYP71AJ51 catalyzed columbianetin to angelicin. Subsequently, the expression profile showed that CYP71AJ49 and CYP71AJ51 were easily affected by environmental conditions, especially UV and temperature. The genes tissue-specific expression and compounds tissue-specific distribution pattern indicated the existence of substance transport in P. praeruptorum. Phylogenetic analysis was conducted with 27 CYP71AJs, CYP71AJ49 and CYP71AJ51 were classified in I-4 and I-2, respectively. These results provide further insight to understand the biosynthetic mechanism of complex coumarins.

Seeds are classified as stimulatory, carminative, anti-inflammatory and extremely useful for vitiligo and leucoderma. Powdered seeds mixed with honey, that has been heated to remove scum, 10 g daily with warm water for fifteen days are claimed to cure vitiligo. It is also used as an emmenagogue to regulate menstruation, as a diuretic, and for the treatment of leprosy, kidney stones, and urinary tract infections. Since ancient times, a tea made from the fruit of Ammi visnaga (khella, as it is known in the Arab world) has been used as a remedy for renal colic due to kidney stones. In Israel and Morocco, the plant is used for the treatment of diabetes. Natural coumarins (furocoumarins), isopimpinellin, xanthotoxin (8-methoxypsoralen, 8-MOP), imperatorin, bergapten, umbelliprenin, maurin, alloimperatorin, ammirin, ammajin and marmesin, have been isolated from the fruits of A. majus. Khellin, visnagin, and khellol glycoside have been isolated from fruits of A. visnaga. 8-MOP is a purified extract of the root, that has been used in a crude form for centuries in the Middle East in the treatment of various skin diseases, and was first utilized in the treatment of vitiligo in 1948. Ethanol seed extract decreased TC, TGs and LDL-C, and increased HDL-C of rats, and also produced significant anti-inflammatory, analgesic, and antipyretic effects. Both a single oral dose and repeated administration of aqueous extract of A. visnaga significantly lowers blood glucose in normal and diabetic rats. Spontaneous passage of multiple ureteral stones in a patient, possibly as a result of using a khellin preparation was reported from Turkey.