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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...

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.

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.

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.

© 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.

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.

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.

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.

Root extracts of Aegle marmelos, an evergreen tree indigenous to India, is an important ingredient in Ayurvedic preparations used for the treatment of pulmonary tuberculosis. Leaves of the tree are used as a remedy for respiratory ailments in folk medicine. The fruit is extensively used in the treatment of various bacterial diseases such as dysentery, diarrhea, etc. The present study was designed to screen organic solvent extracts of fruits of A. Marmelos for their inhibitory activity on Mycobacterium tuberculosis (M. tuberculosis), and to isolate and identify the compounds responsible for antimycobacterial activity. The minimum inhibitory concentration (MIC) of the extract and purified molecules on virulent laboratory strain M. tuberculosis H37Rv was determined by resazurin microtiter assay (REMA). Structural elucidation of the compounds was carried out employing NMR. Cytotoxicity of the compounds was evaluated against human monocyte THP1-derived macrophages by MTT assay. The hexane extract of A. marmelos fruits inhibited the growth of M. tuberculosis at an MIC of 50 μg/mL. Fractionation of the hexane extract by column chromatography led to the isolation of imperatorin, β-sitosterol, plumbagin, marmesin, marmin, and stigmasterol which individually inhibited the growth of M. tuberculosis. In vitro cytotoxicity assay revealed that the compounds are not cytotoxic at the concentrations that inhibited the growth of M. tuberculosis.

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.

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.

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.

Ethnopharmacological relevance Saposhnikovia divaricata (family Apiaceae) a traditional medicinal plant distributed in many provinces of China, is well known for the pharmaceutical value and has been used for rheumatic arthritis, and anxiety in children. Antiviral, antioxidant and antiproliferative activities were also mentioned. The application of this plant are recorded in the Chinese Medicine (CM) classical text the Shen Nong's Materia Medica (Shen Nong Ben Cao Jing). In this monograph S. divaricata (syn Radix Ledebouriella divaricata) is graded as a premium-grade herb, with their broad-spectrum of therapeutic applications for the treatment of cough, common cold, arthralgia, as well as in rheumatic disorders. Aim of the study To isolate and identify chemical constituents (chromones and coumarins) from S. divaricata, collected in Buryatia and Mongolia and to study their in vitro anticancer activity against MEL-8, U-937, DU-145, MDA-MB-231 and ВТ-474 cell lines. Materials and methods An 40% aqueous ethanol extract of the roots of S. divaricata was prepared and further successively fractionated by extraction with petroleum ether, diethyl ether, tert-butyl methyl ether and ethyl acetate. The obtained extracts were subjected to a series of chromatographic separations on silica gel for isolation of individual compounds. Isolated compounds were tested for their cytotoxicity with respect to model cancer cell lines using the conventional MTT assays. Results : Total of 15 individual compounds: coumarins scopoletin 2, bergapten 3, isoimperatorin 4, marmesin 5, (+)-decursinol 9, (−)-praeruptorin B 10, oxypeucedanin hydrate 11, chromones: hamaudol 6, cimifugin 7, 5-О-methylvisamminol 8, chromone glycosides: prim-O-glucosylcimifugin 12, sec-O-glucosylhamaudol 13, 4′-O-β-D-glucopyranosyl-5-О-methylvisamminol 14, 4′-O-β-D-glucopyranosylvisamminol (15) and also polyyne compound panaxinol 1 were isolated and characterized. The structure of dihydropyranocoumarin 10 was confirmed by X-ray diffraction analyses. HPLC-UV method was used for determination of the content of most abundant chromones 7, 12 and 14 in the roots of S. divaricata, collected in Mongolia. Compounds 3–11 and 13, 14 were evaluated for their cytotoxicity with respect to model cancer cell lines. All the compounds were non-toxic in the hemolysis test. Conclusion : This report about the phytochemical profiles of S. divaricata growing in Mongolia and Buryatia led to the identification of 14 compounds including coumarins and chromones. The available coumarins and chromones may serve as new leads for the discovery of anticancer drugs.

Bioactive substances that promote neurite outgrowth and prevent neuronal degeneration are potentially useful for the medical treatment of Alzheimer's disease (AD). This study aimed to obtain bioactive compounds from the stems of the medicinal and edible plant Melicope pteleifolia that promote neurite outgrowth. A bioassay-guided phytochemical investigation led to the isolation of four new chroman derivatives, pteleifolones A–D ( 1 – 4 ), and nine known components, acronyculatin B ( 5 ), acronylin ( 6 ), marmesin ( 7 ), 5-methoxymarmesin ( 8 ), (+)-peucedanol ( 9 ), atanine ( 10 ), N -methylatanine ( 11 ), dictamnine ( 12 ), and evolitrine ( 13 ). Their structures were established by extensive nuclear magnetic resonance (NMR) spectroscopic data analysis. Most of these compounds promoted nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. These chemical and biological results provide a basis for the further development and utilization of M. pteleifolia as a functional food.

Eleven coumarins named osthole (1), imperatorin (2), bergapten (3), prantschimgin (4), grandivitinol (5), suberosin (6), xanthotoxin (7), felamidin (8), marmesin (9), umbelliferone (10), ulopterol (11), and a sterol mixture consisted of stigmasterol (12), β-sitosterol (13) were isolated from the roots of Ferulago blancheana, F. pachyloba and F. trachycarpa through in vitro bioassay-guided fractionation processes. The extracts and bioactive compounds were evaluated for their α-amylase and α-glucosidase activities. Among the tested compounds, felamidin and suberosin showed significant α-glucosidase inhibitory activity with IC50 values of 0.4 and 0.9 mg/mL, respectively, when compared to the reference standard acarbose (IC50 = 4.9 mg/mL). Grandivitinol (IC50 = 20.0 mg/mL) had the lowest inhibitory effect. On the other hand, none of the tested extracts were found to be active on α-amylase inhibition. This is the first report on isolation, characterization of the bioactive compounds and evaluation the α-amylase and α-glucosidase inhibitory activities of these species.Video Clip of Methodology:8 min 26 sec: Full Screen Alternate

Furanocoumarins, such as psoralen, xanthotoxin and bergapten, serve as protectants against phytopathogens and are used in pharmaceutical applications e.g. as DNA-crosslinking agents against non-melanoma skin cancers. Poison hemlock plants (Conium maculatum L.) are a known source of furanocoumarins and toxic alkaloids, but systematic research on callus and suspension cultures with the aim of eliciting secondary metabolites is lacking. Therefore callus cultures of poison hemlock were induced with 0.186 mg L−1 6-benzylaminopurine and 2 or 4 mg L−1 naphthalene acetic acid on McCown’s Woody plant medium. A broad variety of elicitors (alginic acid, cellulase, chitosan, ethylene, methyl jasmonate, salicylic acid, copper(II) sulphate and silver nitrate) were tested with an established cell suspension culture for their capacity to trigger differential metabolite accumulation. Samples were extracted and analysed by gas chromatography-mass spectrometry. Elicitation with alginic acid, cellulase, chitosan, silver nitrate and copper(II) sulphate induced furanocoumarins. Plant hormones (ethylene, methyl jasmonate and salicylic acid) were not able to induce furanocoumarins. Extracts contained bergapten, columbianetin, isopimpinellin, marmesin, oroselone, psoralen and xanthotoxin but not piperidine alkaloids. The relative amount of furanocoumarins was generally higher in the medium than in the cells. The report describes the angular furanocoumarins oroselone and columbianetin together with the linear furanocoumarin marmesin, elicited for the first time in poison hemlock.

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.

It was shown that the plant Peucedanum baicalense (Redow.) Koch is the source of valuable coumarins. Five linear furocoumarins - isoimperatorin, fellopterin, 8-(1,1-dimethylallyloxy) bergapten, deltoin and marmesin were isolated from the roots of Peucedanum baicalense (Redow.) Koch. The structures of these compounds were elucidated by spectroscopic methods. The cytotoxicity of isoimperatorin, fellopterin, 8-(1,1-dimethylallyloxy)bergapten and deltoin was studied on models of human СEM-13, MT-4 and U-937 tumor cells. Compound 8-(1,1- dimethylallyloxy)bergapten had the greatest cytotoxicity.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that a pair of tumors in Fig. 10 appeared to have been duplicated, although one of the tumors appeared at a larger size in the figure relative to the first one. Furthermore, the flow cytometric plots shown in Fig. 2B in the above paper appeared to be remarkably similar to data presented in a paper published in Phytomedicine [Sui C‑G, Meng F‑D and Jiang Y‑H: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC‑7901) cells. Phyomedicine  22: 796‑806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Oncology Reports 39: 597‑602, 2018; DOI: 10.3892/or.2017.6147].

Myocardial infarction (MI) is a leading major health problem with increased morbidity and mortality worldwide. The present study investigates isoproterenol (ISO) induced MI and the beneficial role of Aegle marmelos fruit extract (AMFE) in rats. Our results indicated the significant augmentation of plasma nitric oxide (NOx) levels, C-reactive protein (CRP), homocysteine, apolipoprotein B (apo-B), cardiac tissue lipid peroxidation and liver 3-hydroxy-3 methyl glutaryl CoA (HMG-CoA) reductase activity in ISO treated rats (85mg/kg b.wt) with a concomitant decrease in plasma apolipoprotein A1 (apo-A), lipase activity, paraoxonase-1 activity and cardiac tissue taurine levels when compared with controls. However, pretreatment of ISO administered rats with AMFE (150mg/kg b.wt/day for 45 days) markedly brought the observed alterations toward near normal level indicating its protective role against MI. Further, we have extended our studies to study the interaction of important phytocompounds, marmesin, marmin, umbelliferone and impertonin, present in AMFE with key enzymes, HMG-CoA reductase, iNOS, lipoprotein lipase and paraoxonase using AutoDock4. Molecular docking analysis indicated that HMG-CoA reductase, inducible nitric oxide synthase (iNOS) and lipoprotein lipase formed a strong enzyme ligand complex with impertonin. While the marmesin showed strong interaction with paraoxonase enzyme. In conclusion, our results suggest that AMFE acts as a strong protective agent against ISO-induced MI, and the bioactive compounds are responsible for this protective action which is confirmed by molecular docking studies.

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.

Objective. This study evaluates hepatoprotective potential of Feronia limonia stem bark (FSB) extracts and fractions using experimental models. Materials and methods. Activity levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and cell viability were evaluated in HepG2 cells treated with carbon tetrachloride (CCl4) in presence or absence of FL extracts or fractions. Also, plasma markers of hepatic damage, hepatic antioxidants, lipid peroxidation and histopathological alterations were assessed in rats treated with CCl4 alone or in combination with 200 or 400 mg/kg bodyweight (BW) of FSB-7 or 25 mg/kg BW of silymarin. Results. In vitro co-supplementation of FSB extracts or fractions recorded varying degree of hepatoprotective potentials. Also, pre-supplementation of FSB methanolic extract (FSB-7) followed by CCl4 treatment significantly prevented hepatic damage and depletion of cellular antioxidants. Also, CCl4+ FSB-7 group showed minimal distortion in the histoarchitecture of liver and results were comparable to that of CCl4+ silymarin treated rats. Conclusion. This inventory is the first scientific report on hepatoprotective potential of FSB methanolic extract.

Conchocarpus fontanesianus (A. St.-Hill.) Kallunki & Pirani, Rutaceae, popularly known as pitaguará, is a native and endemic tree from São Paulo and Rio de Janeiro States, Brazil. Based in the information that anticholinesterasic derivatives could act as new prototypes to treatment of Alzheimer disease, this work describes the fractionation guided by evaluation of the anticholinesterase activity of the ethanolic stems extract from C. fontanesianus. This procedure afforded the alkaloids dictamnine (1), γ-fagarine (2), skimianine (3), and 2-phenyl-1-methyl-4-quinolone (4), as well as the coumarin marmesin (5).

Angelica gigas obtained from different geographical regions was characterized using (1)H nuclear magnetic resonance (NMR) spectroscopy and ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) followed by multivariate data analyses. Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) score plots from (1)H NMR and UPLC-MS data sets showed a clear distinction among A. gigas from three different regions in Korea. The major metabolites that contributed to the discrimination factor were primary metabolites including acetate, choline, citrate, 1,3-dimethylurate, fumarate, glucose, histamine, lactose, malate, N-acetylglutamate, succinate, and valine and secondary metabolites including decursin, decursinol, nodakenin, marmesin, 7-hydroxy-6-(2R-hydroxy-3-methylbut-3-ethyl)coumarin in A. gigas roots. The results demonstrate that (1)H NMR and UPLC-MS-based metabolic profiling coupled with chemometric analysis can be used to discriminate the geographical origins of various herbal medicines and to identify primary and secondary metabolites responsible for discrimination.

In addition to the previously known coumarin constituents (xanthotoxin, imperatorin, bergapten, isopimpinellin and marmesin) of Ammi majus L. fruits, a further product has been isolated. On the basis of chemical and physical evidence, the new component was proved to be isoimperatorin (VII).

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.

Five kinds of coumarin compounds were successfully purified from Angelica gigas Nakai by using recyclingpreparative HPLC and identified as decursin (1), decursinol angelate (2), 7-demethylsuberosine (3), marmesin (4), and decursinol (5) by NMR analyses. None of the purified compounds in ethanol showed DPPH radical scavenging activity, while the A. gigas extract (AGNEX) displayed a significant level of activity. Interestingly, compounds 3 in phosphate buffered saline (PBS) showed good ABTS + radical scavenging activity (IC 50 =8.1 ㎍/mL) as did compounds 4 and 5. The anti-inflammatory activities of the purified compounds were evaluated and compared using the NO concentration assay and western blot analysis on LPS-stimulated RAW 264.7 cells. NO production was significantly suppressed by all the compounds in a dose-dependent manner among which compounds 1, 2, and 3 showed very good activities with IC 50 values of 7.4, 6.5, and 7.6 ㎍/mL, respectively. Treatment with compounds 1-5 effectively suppressed the expression levels of iNOS, IL-1β, and COX-2, which are responsible for promoting the inflammatory process. Thus, the ethanol extract and coumarin compounds of A. gigas Nakai hold promise for use as potential anti-inflammatory agents.

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.

A new butenylflavanone, (2S)-5-hydroxy-7-methoxy-8-[(E)-3-oxo-1-butenyl]flavanone (1), and a new rotenoid, 4',5'-dihydro-11,5'-dihydroxy-4'-methoxytephrosin (2), as well as three active flavonoids of previously known structure, isoliquiritigenin (3), genistein (4), and chrysoeriol (5), along with nine known inactive compounds, alpha-toxicarol (6), sumatrol, 6a,12a-dehydro-alpha-toxicarol, 11-hydroxytephrosin, obovatin, marmesin, lupenone, benzyl benzoate, and benzyl trans-cinnamate, were isolated from an ethyl acetate-soluble extract of the stems of Tephrosia toxicaria, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. All isolates were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction. Selected compounds were tested in a mouse mammary organ culture assay to evaluate the inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesions.

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.

The present study describes the effect of a Phytophthora sojae 25-amino acid oligopeptide (Pep25) elicitor on the secondary metabolism of parsley cell cultures ( Petroselinum crispum L.). HPLC analysis of the accumulated compounds in the elicitor-treated cultures revealed the expected accumulation of furanocoumarins (e.g. marmesin and bergapten) as well as various non-coumarin compounds which have not been described previously to occur in this cell culture. These compounds were isolated by preparative HPLC and identified by spectroscopic methods (MS, NMR) as 5-hydroxy- and 7-hydroxy-3-butylidenephthalides including two novel conjugates of the 7-hydroxy derivative, i.e. 7- O -glucoside and 7- O -(6′-malonylglucoside).

Eight new coumarin glycosides were isolated from the methanolic extract of the root and rhizoma of Glehnia littoralis FR. SCHMIDT ex MIQ. (Umbelliferae; "hamabofu" in Japanese). From the results of spectral investigation, they were characterized as glycosides of (S)-peucedanols, (S)-7-O-methylpeucedanols, marmesin and hydroxyimperatorin derivatives, respectively.

Stereoselective syntheses of deuterium labelled marmesins 3a-3e as metabolic probes for biosynthetic studies are described. Starting from iodo-umbelliferone (5), the title compounds were readily available by copper catalysed alkylation-cyclisation and subsequent transfer-hydrogenation of the resulting furanocoumarins 6a-6e. The bioconversion of marmesin by a microsomal preparation of A. majus yielded psoralene (4) and acetone in a single step and proceeded as a syn-elimination of the alkoxy-substituent together with a single hydrogen atom from a vicinal carbon atom (β-cleavage).

Cells of three different plant species were immobilized on a glass fiber fabric by sol-gel deposition. The process involved the following steps: (1) reinforcement of glass-fiber supports by coating with a gelling solution of hybrid-SiO2 precursors, (2) entrapment of cells by stuffing the voids of the support with a suspension cell culture, (3) achievement of a definite immobilization by a primary treatment with SiO2-sol, followed by gas phase reaction of tetraethoxysilane and diethoxymethylsilane with OH groups of cell wall and of surface silica. Immobilized cells maintained their viability as tested by the positive reaction to TTC and by the development of calli from stretched samples. The samples did not release cells in solution over a time period of four months, at least. The biosynthetic capability of one of immobilized species, Coronilla vaginalis, was studied by periodically monitoring the production of umbelliferone and marmesin which constituted the major secondary metabolites produced by in vitro cultured cells of this species. The results were evaluated in order to determine the versatility of the method and its potential for exploitation in continuous industrial-scale production of rare and fine chemicals.

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

Examination of the aerial parts of Boronia algida has led to the isolation of six coumarins, an alkaloid and a triterpene. The coumarins were identified as ( + )-marmesin, 7-demethylsuberosin, 5-deoxyprotobruceol-II hydroperoxide, a mixture of the diastereomers of 5-deoxyprotobruceol-III 3′ξ-hydroperoxide and 3′-hydroxyxanthyletin; the alkaloid as 1-methyl-2-pentadecyl-4(1H)-quinolone and the dammarane triterpene as (E)-25-hydroperoxy-3β-hydroxydammar-20,23-diene. The latter compound and 3′-hydroxyxanthyletin are novel natural products. The chemotaxonomic significance of these isolates in the genus Boronia is discussed.