Murragleinin,a coumarin from Murraya gleinei leaves

A new trioxygenated C-8 prenylated coumarin, 5,6,7-trimethoxy-8-(2′,3′-dihydroxyisopentenyl)-coumarin and the laevorotatory form of mexoticin, sibiricin and phebalosin were isolated from the leaves of Murraya gleinei together with the coumarins meranzin hydrate, meranzin, murralongin, murrangatin and scopoletin, the flavone exoticin, the alkaloid skimianine and the sterol stigmasterol.     

Cedkathryns A and B, pentanortriterpenoids from Cedrelopsis gracilis (Ptaeroxylaceae)

The stem bark of Cedrelopsis gracilis (Ptaeroxylaceae) has yielded three known prenylated coumarins, O-methylalloptaeroxylin, ptaerochromenol and umtatin and the novel pentanortriterpenoids, cedkathryn A and cedkathryn B.     

Cancer chemopreventive constituents from Melicope lunu-ankenda

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.     

Umbelliferone derivatives exert neuroprotective effects by inhibiting monoamine oxidase A,self-amyloidβ aggregation,and lipid peroxidation

Umbelliferone has been demonstrated to have a wide range of biological activities. However, the effect of incorporating a formyl moiety in the umbelliferone scaffold has not been investigated. In this paper, we investigated the inhibitory activity of six coumarins, namely umbelliferone (1), 6-formyl umbelliferone (2), 8-formyl umbelliferone (3), umbelliferone-6-carboxylic acid (4), esculetin (5), and scopoletin (6) against human monoamine oxidases (hMAOs), self-amyloid β (Aβ) aggregation, and lipid peroxidation. We found that all compounds had high selectivity for hMAO-A in comparison with hMAO-B. Among the compounds, 2 exhibited the highest hMAO inhibitory activity with an IC₅₀ value of 3.23 µM for hMAO-A and 15.31 µM for hMAO-B. Enzyme kinetic analysis showed that 2 and 3 were competitive hMAO inhibitors. In silico hydrated molecular docking simulations revealed that the coumarins interacted with substrate-binding site residues of the enzymes and the isoalloxazine ring of FAD. In addition, formyl coumarins 2 and 3 significantly inhibited lipid peroxidation in rat brain homogenates and self-Aβ_25-35 aggregation compared to other derivatives. These represent the first experimental and modelling data for hMAO-A/B inhibition by umbelliferone derivatives. Together, the data suggest that introduction of a formyl moiety in the 7-hydroxycoumarin scaffold, especially at the 6 position, plays an important role in the inhibition of hMAOs, Aβ self-aggregation, and lipid peroxidation. Umbelliferone derivative 2 is a promising therapeutic lead scaffold for developing anti-neuropsychiatric disorder drugs that function via selective hMAO-A inhibition.     

Triterpenoids and coumarins from the leaves of calophyllum cordato-oblongum

The hot light petrol extractives of the leaves of Calophyllum cordato-oblongum gave D:A-friedo-oleanan-3-one, 28-hydroxy-D:A-friedo-oleanan-3-one (canophyllol) and three new coumarins: cordatolides A and B and oblongulide.     

Produits neutres et alcaloides de Myrtopsis macrocarpa,M. myrtoidea,M. novae-caledoniae et M. sellingii

Stems and leaves of Myrtopsis macrocarpa, M. myrtoidea, M. novae-caledoniae and M. sellingii yielded terpenes, sterols, coumarins, alkaloids (furoquinolines and quinolones) and amides. A new quinolone (8-methoxy flindersine) occurs in Myrtopsis macrocarpa, a new amide (N-benzoyltryptamine) in M. myrtoidea, two new coumarins (myrsellin and myrsellinol) and a new dihydrofuroquinoline (myrtopsine) in M. sellingii. Structures of the new compounds are proposed from chemical and spectroscopic evidence.     

Dereplication of Mammea neurophylla metabolites to isolate original 4-phenylcoumarins

Mammea coumarins are isoprenylated 4-alkyl or 4-phenylcoumarins. Their distribution is limited to 3 Clusiaceae/Calophyllaceae genera. We recently reported on their presence in Mammea neurophylla bark extracts, where they exhibited anti-AGE properties associated with a prevention of the endothelial dysfunction. About 120 mammea coumarins were already described so, in order to focus further phytochemical analysis on original or bio-active compounds, we developed a methodology to facilitate the detection and identification of compounds of interest. Our aim was to develop a LC-DAD–ESI-MSⁿ method for rapid, sensitive and simple analysis of the mammea coumarins in calophyllaceous/clusiaceous species. For that, full LC-DAD–MSⁿ data were acquired from 11 4-phenylcoumarins previously isolated in our laboratory. Bark, leaves and fruits of M. neurophylla were then extracted with DCM using an ASE apparatus. Extracts were finally analyzed through LC-DAD–HRMSⁿ and UV and MS profiles were compared to our database as well as literature data. Detected new compounds were isolated and their structures elucidated through ¹H, ¹³C and 2D NMR analysis. Finally, 24 known mammea coumarins were dereplicated from bark, leaf and fruit DCM extracts of M. neurophylla and the structure of 4 unreported compounds could be predicted. In particular, the structures of mammea A/AA 9-hydroxyCycloF and mammea A/AB 9-hydroxyCycloF were confirmed after purification and extensive NMR analyses. By comparison of UV and mass fragmentation data from a small library of reference compounds, LC-DAD–HRMSⁿ analysis of mammea coumarins in crude extracts allows the structure prediction of novel or bio-active compounds. This useful guiding-tool could be easily applied to other Clusiaceae/Calophyllaceae phytochemical analysis.     

Naturally occurring prenylated coumarins from Micromelum integerrimum twigs

A phytochemical investigation of secondary metabolites from Micromelum integerrimum was reported. Two new prenylated coumarins named as hydramicromelin D (1) and integerrimelin (2) were isolated along with 9 known coumarin derivatives. The chemical structures as well as relative stereochemistries of those coumarins were confirmed on the basis of extensive spectroscopic data interpretation and comparison with those previously published data.     

The coumarins of Philotheca sensu lato: distribution and systematic significance

Five coumarins and two flavonoid glycosides are reported from Philotheca pinoides of which one, 3-(3-hydroxy-3-methylbut-1-enyl)-7,8-dimethoxycoumarin, appears to be novel. HPLC analysis of extracts of a number of other Philotheca species revealed that 5,7-dioxygenated-6,8-prenylated coumarins were present in P. apiculata, P. coccinea, P. deserti, P. pachyphylla, P. rhomboidea, P. thryptomenoides and P. gardneri, but not in P. nodiflora, P. pinoides, P. sericea, P. spicata, P. tomentella or P. woganensis. An analysis of the distribution of coumarins demonstrate that Geleznowia verrucosa is chemically indistinguishable from many species of Philotheca section Philotheca, whereas Philotheca section Erionema is more variable. Typical avicennol type coumarins have been found in the Boronieae only in Philotheca section Philotheca, in Geleznowia and in one species of Asterolasia. Coumarins that characterise Philotheca section Philotheca are not currently known from Eriostemon s.s., and sympatric genera such as Phebalium and Drummondita.     

Discovery of 2,4-thiazolidinedione-tethered coumarins as novel selective inhibitors for carbonic anhydrase IX and XII isoforms

Different 2,4-thiazolidinedione-tethered coumarins 5a–b, 10a–n and 11a–d were synthesised and evaluated for their inhibitory action against the cancer-associated hCAs IX and XII, as well as the physiologically dominant hCAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins 10a, 10 h, and 2-thienyl/furyl-bearing coumarins 11a–c exhibited the best hCA IX (K_Is between 0.48 and 0.93 µM) and hCA XII (K_Is between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target hCA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins 10a, 10 h and 11a–c, were assessed in an in vitro antiproliferative assay, and then the most potent antiproliferative agent 11a was tested to explore its impact on the cell cycle phases and apoptosis in MCF-7 breast cancer cells to provide more insights into the anticancer activity of these compounds.     

Genetic alterations for increased coumarin production lead to metabolic changes in the medicinally important Pelargonium sidoides DC (Geraniaceae)

The medicinal plant Pelargonium sidoides is fast becoming threatened due to the overharvest of its tubers from the wild to produce a phytopharmaceutical for treating respiratory infections. The action of the coumarins is implicated in the efficacy of the commercial herbal extract with the highly oxygenated coumarins exhibiting the best anti-bacterial and anti-viral activity. Through this work we aimed at exploring the metabolic effects of Agrobacterium rhizogenes transformation. After confirmation of transgenesis using PCR amplification of the rol A (320 bp), rol B (400 bp) and rol C (600 bp) genes, metabolite profiles indicated a high level of variability between the different transgenic clones but these had more compounds compared to non-transgenic control cultures. This was represented by a two- to four-fold increase in detected metabolites in transgenic clones. We quantified several commercially important coumarins, flavonoids and phenolic acids. One of the clones had six out of nine of these metabolites. Overall, the concentration of these metabolites of interest were significantly changed in transgenic root cultures, for instance shikimic acid was recorded at the highest level in clone A4T-A. Production of key metabolites at significantly higher concentrations due to transgenesis and positive anti-bacterial activity exhibited by transgenic roots lends support to the idea of developing these clones as an alternative source that will allow for sustainable access to economically valuable secondary compounds of P. sidoides.     

Phytochemical investigation on the fruits of Camptotheca acuminata and their chemotaxonomic significance

A phytochemical investigation on the fruits of Camptotheca acuminata led to the isolation of 13 compounds, including five coumarins (1–5), two alkaloids (6 and 7), two triterpenoids (8 and 9), three lactones (10–12) and a sesquiterpene (13). The structures of these compounds were elucidated by extensive spectroscopic methods and comparion with literature data. All compounds were isolated from the Nyssaceae family for the first time. Additionally, it should be noted that this is the first report of coumarins in the C. acuminata. The chemotaxonomic significance of the isolated compounds was summarised.     

Comparison of seven structurally related coumarins on the inhibition of Quorum sensing of Pseudomonas aeruginosa and Chromobacterium violaceum

Quorum sensing (QS) is a cell-to-cell signaling communication system that controls the virulence behavior of a broad spectrum of bacterial pathogens, participating also in the development of biofilms, responsible of the antibiotic ineffectiveness in many infections. Therefore, QS system is an attractive target for antimicrobial therapy. In this study, we compare the effect of seven structurally related coumarins against bacterial growth, biofilm formation and elastase activity of Pseudomonas aeruginosa. In addition, the anti-pathogenic capacity of the seven coumarins was evaluated on the wild type and the biosensor strain of Chromobacterium violaceum.The comparative study of coumarins showed that molecules with hydroxyl groups on the aromatic ring displayed higher activity on the inhibition of biofilm formation of P. aeruginosa over coumarins with substituents in positions 3 and 4 or without the double 3,4-bond. These 3 or 4-hydroxylated positions caused a decrease in the anti-biofilm activity obtained for coumarin. However, the hydroxyl group in position 3 of the pyrone ring was important for the inhibition of C. violaceum QS and elastolytic activity of P. aeruginosa. The effects observed were active independently of any effect on growth. According to our results, coumarin and its hydroxylated derivatives represent an interesting group of compounds to use as anti-virulence agents against the human pathogen P. aeruginosa.     

New 5-Methylcoumarin derivatives from Ethulia conyzoides

A reinvestigation of the aerial parts of E. conyzoides L. afforded three new 5-methyl coumarins and a degraded nor compound with an eucarvone part. The structures were elucidated using spectral methods and some chemical transformations. The biogenetic relationships of these compounds are discussed.     

Counlarins,limonoids and an alkaloid from Clausena excavata

In addition to a known alkaloid, some limonoids and coumarins, the new coumarins excavatins A–M have been isolated from Clausena excavata. Their structures have been assigned by NMR and CD investigations.     

Comparative analysis of root anatomical structure,chemical components and differentially expressed genes between early bolting and unbolting in Peucedanum praeruptorum Dunn

Early bolting of Peucedanum praeruptorum Dunn severely affects its quality. In this study, we compared with the root structure of P. praeruptorum and its four coumarins content between early bolting (CT) and unbolting (WT) at different growth stages. We found that the proportion of area outside the root cambium (Rs) was higher in the WT plants than in the CT plants and correlated positively with the proximity to the root tip. Furthermore, the content of all four coumarins was also higher in the WT plants relative to the CT plants. In addition, we identified 15,524 differentially expressed genes (DEGs) between the two plant varieties. 11 DEGs are involved in the photoperiod and gibberellin pathways that regulate early bolting and 24 genes involved in coumarins biosynthesis were also identified. Nevertheless, early bolting of P. praeruptorum does affect its quality formation, and further studies are needed to confirm its mechanism.     

Phenolic constituents of Artemesia tridentata spp. Vaseyana

Ten coumarins and four flavonoids have been isolated from a single collection of Artemesia tridentata ssp. vaseyana (Rydb.) Beetle. The coumarins are 7-methylesculin, esculin, umbelliferone, skimmin, cichoriin, isoscopoletin, scopoletin, scoparon, esculetin and a new natural product, artelin (5,6,7,8-tetramethoxy coumarin). The flavonoids are luteolin, luteolin-7-glucoside, axillarin and eupafolin.     

New coumarins from Coleonema album

Six coumarins have been isolated from the aerial parts of Coleonema album and identified as ulopterol, 7-(3′, 3′-dimethylallyloxy)-coumarin, (R)-(+)-2′,3′-epoxy-suberosin, and the novel coumarins (R)-(+)-7-(2′, 3′-epoxy-3′-methylbutoxy)-coumarin, (R)-(+)-7-(2′,3′-dihydroxy-3′-dihydroxy-3′-methylbutoxy)-coumarin and (R)-(+)-7-methoxy-8-(2′,3′-epoxy-3′-methylbutoxy)-coumarin.     

Linear furocoumarins and other constituents from thamnosma texana

Eight linear furocoumarins and three coumarins were isolated and identified from Thamnosma texana. They were xanthotoxin, imperatorin, bergapten, alloimperatorin methyl ether epoxide, heraclenin, isopimpinellin, psoralen, oxypeucedanin, and the coumarins herniarin, osthol and thamnosmin. The linear furocoumarins appear to be agents that account for the known photosensitizing properties of Thamnosma texana, and consequently its colloquial name, ‘blisterweed.’ This is the first report on the occurrence of imperatorin, heraclenin, oxypeucedanin, herniarin or osthol in any Thamnosma species.     

A new coumarin from Ferula loscosii and the correct structure of coladonin

From the roots of Ferula loscosii the coumarins umbelliprenin, coladin and coladonin and the new natural isovaleryl derivative of the latter have been isolated. A study which confirms the structure of coladonin and its difference from farnesiferol A is also given.