Pentadecaibins I-V: 15-Residue Peptaibols Produced by a Marine-Derived Trichoderma sp. of the Harzianum Clade.

In the course of investigations on peptaibol chemodiversity from marine-derived Trichoderma spp., five new 15-residue peptaibols named pentadecaibins I-V (1-5) were isolated from the solid culture of the strain Trichoderma sp. MMS1255 belonging to the T. harzianum species complex. Phylogenetic analyses allowed precise positioning of the strain close to T. lentiforme lineage inside the Harzianum clade. Peptaibol sequences were elucidated on the basis of their MS/MS fragmentation and extensive 2D NMR experiments. Amino acid configurations were determined by Marfey's analyses. The pentadecaibins are based on the sequences Ac-Aib1-Gly2-Ala3-Leu4-Aib/Iva5-Gln6-Aib/Iva7-Val/Leu8-Aib9-Ala10-Aib11-Aib12-Aib13-Gln14-Pheol15. Characteristic of the pentadecaibin sequences is the lack of the Aib-Pro motif commonly present in peptaibols produced by Trichoderma spp. Genome sequencing of Trichoderma sp. MMS1255 allowed the detection of a 15-module NRPS-encoding gene closely associated with pentadecaibin biosynthesis. Pentadecaibins were assessed for their potential antiproliferative and antimicrobial activities.

Brevipedicelones D and E, Two C-O-C Flavonoid Dimmers from the Leaves of Garcinia brevipedicellata and Anti-onchocercal Activity.

A novel isoflavone-chromone flavonoid C-O-C dimmer, brevipedicelone D (1), along with one new C-O-C biflavonoid derivative, brevipedicelone E (2), were isolated from the ethyl acetate extract of the leaves of Garcinia brevipedicellata, a medicinal plant used in folk medicine in parts of Cameroon. Their structures were elucidated by extensive spectroscopic techniques, including 1D- and 2D- NMR, MS experiments, as well as comparing their spectral data with those of known analogues. Anti-onchocercal screening of 1 showed moderate inhibition of adult worm motility of Onchocerca ochengi by 60% at the highest concentration (20 µg/mL) and inhibited motility of both the juvenile worms of O. ochengi and Loa loa by 90% at this same concentration.

Chemical constituents of the leaves of Campylospermum elongatum.

The leaves of Campylospermum elongatum have furnished the cyano-glycoside (lithospermoside), nine isomeric biflavonoid derivatives among which five are I3-II6 linked (robustaflavone; 4'-O-methyl robustaflavone; 4',4″'-di-O-methyl robustaflavone; 7,4',4″-tri-O-methyl robustaflavone; 4',7″-di-O-methyl robustaflavone) and four I3-II8 linked (amentoflavone; 7-O-methyl amentoflavone; 7,7″-di-O-methyl amentoflavone; 7, 4',7″-tri-O-methyl amentoflavone) and a flavone glycoside, 4″-O-methyl-7-O-ß-d-galactosylapigenin. All structures were established from a complete spectroscopic analysis (MS, IR, 1D, and 2D NMR, including HSQC, HMBC, and NOESY) as well as by comparing the obtained spectroscopic data with literature. This is the first report on the characterization of 4'-O-methyl-7-O-ß-d-galactosylapigenin from the genus campylospermum and thus has important chemotaxonomic implications.

New flavonoid C-O-C dimers and other chemical constituents from Garcinia brevipedicellata stem heartwood.

The methanol extract of the stem heartwood of Garcinia brevipedicellata has furnished three new flavonoid C-O-C dimers, brevipedicilones A (6), B (8) and C (10), along with five previously reported flavonoid dimers, viz. amentoflavone (1), 4″'-O-methylamentoflavone (2), robustaflavone (3), 4'-O-methyl robustaflavone (4) and tetrahinokiflavone (5). The new structures, which are composed of flavanone-flavanonol or flavanonol-flavanonol sub-units, were established based on spectroscopic analysis including 1D and 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY) spectroscopy, and by comparing their spectral data with those reported for related compounds.

A New Geranylated Chalcone from Andrographis lobelioides.

A new O-geranylated chalcone, 2'-hydroxy-2-methoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl] chalcone (1), together with three known flavones, 5-hydroxy-7,2'-dimethoxyflavone (2), skullcapflavone I (3) and echioidin (4), were isolated from the leaves of Andrographis lobelioides. The structure of 1 and the known compounds (2-4) were achieved by extensive 1D and 2D NMR spectral and chemical studies.

Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa.

Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 µM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species.

Structure elucidation and antioxidant activity of the phenolic compounds from Rhynchosia suaveolens.

A new benzophenone, 2-hydroxy-3,4-dimethoxybenzophenone (1), together with a known C-glycosylxanthone, mangiferin (2) and two known C-glycosylflavones, isovitexin (3) and isoorientin (4), were isolated from the flowers of Rhynchosia suaveolens DC. (Fabaceae). The structure of the new compound (1) and the known compounds (2-4) were elucidated by extensive 1D and 2D NMR spectral studies. The plant extracts, as well as the isolated compounds, were evaluated for their total phenolic content (TPC), total flavonoid content (TFC) and DPPH radical scavenging activity. Among the isolated compounds, mangiferin (2) and isoorientin (4) showed significant radical scavenging activity comparable with that of ascorbic acid.

A new di-C-prenylated coumarin from Sophora interrupta.

A new di-C-prenylated coumarin, 7-methoxy-6,8-bis-(2,3-dihydroxy-3-methylbutyl)-coumarin (1), together with seven known compounds, isopimpinellin (2), an arylbenzofuran (3), three flavonoids (4-6), (+)-maackianin (7) and echinoisoflavanone (8), were isolated from the leaves of Sophora interrupta Bedd. The structure of the new compound 1 as well as known compounds was elucidated by extensive 1D and 2D NMR spectral studies.

Two new chalcones from Clerodendrum phlomidis.

Two new chalcones, 3,2',3'-trihydroxy-4'-methoxychalcone (1) and 3,2'-dihydroxy-4',6'-dimethoxychalcone (2), were isolated from the seeds of Clerodendrum phlomidis together with three known flavonoids, 5-hydroxy-7-methoxyflavanone (3), 5-hydroxy-7-methoxyflavone (4), and kaempferol-3-O-α-l-rhamnopyranoside (5). The structures of the new compounds 1 and 2 have been established mainly on the basis of 1D and 2D NMR studies.

Two new chalcones from the flowers of Clerodendrum inerme.

Two new chalcones, 3-hydroxy-3',4'-dimethoxychalcone (1) and 3,2'-dihydroxy-3',4'-dimethoxychalcone (2), were isolated from the flowers of Clerodendrum inerme (L.) Gaertn together with two known flavones, 7-O-methylwogonin (3) and eucalyptin (4). The structures of the new compounds 1 and 2 have been established by extensive 2D-NMR and ESI-TOFMS studies.

Natural aristolactams and aporphine alkaloids as inhibitors of CDK1/cyclin B and DYRK1A.

In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A.

A new O-prenylated flavonol from the roots of Sophora interrupta.

A new O-prenylated flavonol, 3',4'-dimethoxy-7-(γ,γ-dimethylallyloxy)flavonol (1), together with three known compounds, 2'-hydroxy-3,4-dimethoxychalcone (2), biochanin A (3) and kaempferol-3-O-ß-D-glucopyranoside (4), were isolated from the roots of Sophora interrupta Bedd. The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectral studies.

Two new flavonoids from the seeds of Derris scandens.

Two new flavonoids, (2S)-3',4',5'-trimethoxyflavanone (1) and 2'-hydroxy-2,4-dimethoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl]chalcone (2), together with a known pterocarpene, flemichapparin B (3), and a known rotenoid, dehydrodeguelin (4), were isolated from the seeds of Derris scandens. Their structures were determined by means of extensive 1D and 2D NMR spectral studies.

Flavonoid glycosides and their p-coumaroyl esters from Campylospermum calanthum leaves.

Six new compounds, comprising three flavonoid glycosides and their respective coumaroyl esters, have been isolated and characterized from the methanol extract of the leaves of Campylospermum calanthum, along with three known flavonoid aglycones, 7-O-methyl apigenin (1), 7-O-methyl luteolin (2), and 7-O-methyl quercetin (3). Their structures were elucidated based on chemical evidence as well as spectroscopic analysis including 1D and 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY) spectroscopy and by comparing their spectral data with those reported for related compounds.

Chemical and bioactivity evaluation of the bark of Neonauclea purpurea.

Bioassay-guided fractionation of the MeOH extract from the stem bark of Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2 indole alkaloids, cadambine (1) and alpha-dihydrocadambine (2), as well as a quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with IC50 values of 6.6 and 11.3 microM, respectively. Compounds 1 and 2 showed no cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with an IC50 value of 1.19 microM.

Phytochemical and biological studies of Ochna species.

The genus Ochna L. (Gr, Ochne; wild pear), belonging to the Ochnaceae family, includes ca. 85 species of evergreen trees, shrubs, and shrublets, distributed in tropical Asia, Africa, and America. Several members of this genus have long been used in folk medicine for treatment of various ailments, such as asthma, dysentery, epilepsy, gastric disorders, menstrual complaints, lumbago, ulcers, as an abortifacient, and as antidote against snake bites. Up to now, ca. 111 constituents, viz. flavonoids (including bi-, tri-, and pentaflavonoids), anthranoids, triterpenes, steroids, fatty acids, and a few others have been identified in the genus. Crude extracts and isolated compounds have been found to exhibit analgesic, anti-HIV-1, anti-inflammatory, antimalarial, antimicrobial, and cytotoxic activities, lending support to the rationale behind several of its traditional uses. The present review compiles the informations concerning the traditional uses, phytochemistry, and biological activities of Ochna.

Spiranthenones A and B, tetraprenylated phloroglucinol derivatives from the leaves of Spiranthera odoratissima.

Two new polyprenylated acylphloroglucinols, spiranthenones A (1) and B (2), a sesquiterpenoid, 6 α-acetoxy,1 ß-hydroxyeudesm-4(15)-ene (3), along with sesamin and ß-sitosterol, were isolated from the EtOAc extract of the leaves of Spiranthera odoratissima, and shown to display antiprotozoal activity. Their structures and relative stereochemistry were elucidated by NMR and mass spectrometry. These compounds exhibited moderate antiprotozoal activity, but without significant cytotoxicity against fibroblasts cell line NIH-3T3. Compound 3 was the most selective towards parasites.

Unprecedented occurrence of isoaspartic acid in a plant cyclopeptide.

Three structurally related cycloheptapeptides, cyclocitropsides A-C, have been isolated from a MeOH extract of the root bark of Citropsis articulata, a medicinal plant in Uganda. Their sequences were elucidated on the basis of their MS/MS fragmentation, extensive 2D-NMR, chemical degradation, and biochemical modifications. Surprisingly, the sequence of cyclocitropside C differed from that of cyclocitropside B only by an Asp(5)/isoAsp(5) substitution. This is the first report of an isoAsp residue in a plant cyclic peptide.

Structure and in vitro antiparasitic activity of constituents of Citropsis articulata root bark.

From the results of an ethnomedicinal investigation of plants from Uganda with antimalarial activity, Citropsis articulata was selected because of the antiplasmodial effect of an ethyl acetate extract of its root bark. Thus, from the cyclohexane, ethyl acetate, and methanol extracts, two new heterocyclic compounds, omubioside (1) and katimborine (2), were isolated in addition to five known coumarins (rutarin (3), seselin (4), suberosin (5), demethylsuberosin (6), and haploperoside (7)), two known alkaloids (5-hydroxynoracronycine (8) and 1,5-dihydroxy-2,3-dimethoxy-10-methyl-9-acridone (9)), trigonelline (10), and the limonoid 7α-obacunyl acetate (11). The best growth inhibitors of Plasmodium falciparum were alkaloids 8 and 9, with IC50 values of 0.9 and 3.0 µg/mL.

Potency of inhibition of human DNA topoisomerase I by flavones assessed through physicochemical parameters.

DNA topoisomerases, enzymes involved in DNA replication and transcription, are known as targets for anticancer drugs. Among the various types of topoisomerase inhibitors, flavones (F) have been identified as promising compounds. In this study, it is shown that the potency of flavones acting as topoisomerase I inhibitors can be ranked according to their redox properties and their 3D structure. Linear correlations were observed between the topoisomerase I inhibition activity exerted by five flavones (chrysin, apigenin, kaempferol, fisetin, quercetin) and experimental and theoretical redox parameters of F. Moreover, theoretical calculations of the dihedral angle O(1)-2-1'-2' in the flavone molecules indicate the importance of their structural and steric features in their potency as topoisomerase I inhibitors. It is suggested that the flavones might interact with the DNA-topoisomerase I complex after their oxidation into quinones via autoxidation, enzymatic oxidation, or reactions with reactive oxygen species. Our investigation opens a new strategy quantitatively based on redox and 3D structural parameters in the search for the most active flavones as anticancer drug candidates inhibiting topoisomerase I.