Methoxylated bibenzyls and isoflavones from Baphia massaiensis Taub.

Chemical investigation of the stem bark of Baphia massaiensis Taub. led to the isolation of two new natural compounds named 3-hydroxy-2,5,2'-trimethoxybibenzyl (1) and 2'-hydroxy-2,3,5,6-tetramethoxybibenzyl (2), the latter has been previously reported as a synthetic compound, together with twelve known compounds 3-14. The chemical structures of the isolated compounds were elucidated by using NMR analysis and mass spectrometry, as well as comparisons with the reported data in the literature. Known bibenzyls 3-5, bauhinoxepin J (6), and isoflavones 7-10 and 12-14, were reported from genus Baphia for the first time. The isolated compounds were evaluated for their antibacterial activities in-vitro against Staphylococcus aureus and Escherichia coli. The bioactivity evaluation revealed that bibenzyls 1 and 2 showed weak inhibitory activity with MIC values of 1000 µg/mL against S. aureus and bauhinoxepin J (6) showed moderate inhibitory activity with MIC value of 63 µg/mL against S. aureus.

New isoflavan from Erythrina livingstoniana.

Chemical investigation of the root wood of Erythrina livingstoniana led to the isolation of one previously undescribed isoflavan (3S,3″R)-7-hydroxy-2'-methoxy-[3″-hydroxy-2″,2″-dimethylpyrano (3',4')] isoflavan 1, together with eleven known compounds 2-12. The structure of compound 1 was elucidated on the basis of extensive spectroscopic and spectrometric analyses (1 D and 2 D-NMR and APCI-HRMS), with absolute configurations established by comparison of experimental and DFT calculated ECD data. The assignment of the absolute configurations of C-3 and C-3″ of compounds 2 and 3, respectively, were reported for the first time. Compounds 1 - 4 were evaluated for their antibacterial activities in vitro against E. coli ATCC 25922 and S. aureus ATCC 25923. Compound 1 exhibited moderate antibacterial activity with MIC value of 0.063 mg/mL against the clinically relevant risk-group 2 (RG-2) bacterium S. aureus.

An Update of Erythrinan Alkaloids and Their Pharmacological Activities.

The period of the past 5 years has witnessed a remarkable increase in all of the number, structural variety, and complexity of erythrinan alkaloids reported. This structural diversity seems to be most pronounced in the alkaloids reported from the two species Erythrina arborescens and Erythrina variegata. Between them, work-up of these taxa yielded new polymeric (dimeric and trimeric) erythrinan alkaloids, a first example in one case where a normal 6,5,6,6-membered indoloisoquinoline spirocylic core has rearranged to a spiro-fused 6,5,7,6-skeleton. Furthermore, erythrinan alkaloids with a fifth ring containing a 2H-imidazole functionality were also reported for the first time, together with some new structures having an unusual substitution and with functionalities at positions C-3 and C-7 of the erythrinan core. This contribution has included 40 more erythrinan alkaloids that are either new or were omitted in the most recent major reviews on the same topic, leading to a total of 154 known erythrinan alkaloids to date. There are a few cases where the structures of the new alkaloids are contestable due to insufficient data having been obtained on isolation. To facilitate easier reference and identification, all structures having a common core have been placed in the same table or figure in this chapter.The reported pharmacological activities of the new and known erythrinan alkaloids documented have shown a considerable bias towards central nervous system and related activities. Other prominent activities that have been reported are antifeedant, insecticidal, cytotoxic, antiprotozoal, anti-inflammatory, antioxidant, antifungal, and antiviral effects. Erythrinan alkaloids generally seem to lack antibacterial activity. Several new polymeric alkaloids were found to lack cytotoxicity against a number of human cancer cell lines, although two of them showed moderate aphicidal activity and one exhibited weak to moderate acetylcholinesterase inhibition. The biological activity of erythrinan alkaloids seems to be influenced by basic substructural requirements, such as a conjugated diene (Δ1,2, Δ6,7) system and is modulated by the presence (or absence) of other groups in rings A, B, C, and D of the erythrinan core. The erythrinan core may provide potential leads to structures that eventually may be useful therapeutically.In recent years, a number of stereoselective chemical synthesis methods have been applied towards the erythinan alkaloids, and these are described in this contribution.

Flavanones of Erythrina livingstoniana with antioxidant properties.

Six new flavanones (1-6), together with six known compounds were isolated from Erythrina livingstoniana. Their structures were elucidated on the basis of NMR data and HRMS(n) fragmentation pathway and by comparison with literature data. Compounds 5, 7 and 8 showed remarkable DPPH free radical scavenging efficacies. The compounds, however, did not demonstrate an anti-inflammatory potential when tested using a PGE2 (prostaglandin E2) competitive enzyme immunoassay. The plausible biosynthetic pathways of the isolated compounds are described.

GC-MS Analysis and Preliminary Antimicrobial Activity of Albizia adianthifolia (Schumach) and Pterocarpus angolensis (DC).

The non-polar components of two leguminoceae species Albizia adianthifolia (Schumach), and Pterocarpus angolensis (DC) were investigated. GC-MS analysis of the crude n-hexane and chloroform extracts together with several chromatographic separation techniques led to the identification and characterization (using NMR) of sixteen known compounds from the heartwood and stem bark of Albizia adianthifolia and Pterocarpus angolensis respectively. These constituents include, n-hexadecanoic acid (palmitic acid) 1, oleic acid 2, chondrillasterol 3, stigmasterol 4, 24S 5α-stigmast-7-en-3ß-ol 5, 9,12-octadecadienoic acid (Z,Z)-, methyl ester 6, trans-13-octadecanoic acid, methyl ester 7, tetradecanoic acid 8, hexadecanoic acid, methyl ester 9, octadecanoic acid 10, tetratriacontane 11, 7-dehydrodiosgenin 12, lupeol 13, stigmasta-3,5-diene-7-one 14, friedelan-3-one (friedelin) 15, and 1-octacosanol 16. Using agar over lay method, the preliminary antimicrobial assay for the extracts was carried out against bacterial (E. coli, P. aeruginosa, B. subtilis, S. aueus) and a fungus/yeast (C. albicans) strains. The n-hexane and chloroform extracts of A. adianthifolia showed the best activity against E. coli with minimum inhibition quantity (MIQ) of 1 µg each while the remaining exhibited moderate-to-weak activity against the test microorganisms.

Erylivingstone A-C with antioxidant and antibacterial activities from Erythrina livingstoniana.

The chemical study of Erythrina livingstoniana has led to the isolation of three new flavanones namely 5,7,3'-trihydroxy-4'-methoxy-5'-formylflavanone (erylivingstone A) (1), 5,7,3'-trihydroxy-5'-(2-hydroxy-3-methylbut-3-enyl)-4'-methoxyflavanone (erylivingstone B) (2) and 5,7,3'-trihydroxy-5'-(3-hydroxy-3-methyl-trans-but-1-enyl)-4'-methoxyflavanone (erylivingstone C) (3) together with three known compounds (4-6). Their structures were elucidated on the basis of NMR data, HRMS(n) fragmentation pathway and by comparison with literature data. We evaluated the antibacterial efficacies and free-radical scavenging potential of the isolated compounds (1-6). The typical environmental strains of Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, as well as against the clinically important Staphylococcus aureus, Streptococcus pyogenes and E. coli (risk-group 2) were used for the antibacterial assay. Compounds 5 and 6 exhibited the most pronounced efficacy against tested environmental bacteria as well as against the pathogenic strain of E. coli. Compound 3 was also quite active against these three bacterial strains. The isolated compounds showed weak radical scavenging properties with compound 6 being the most active, followed by compounds 2, 3 and 5.

Three new isoflavonoids from Erythrina caffra.

Three new isoflavonoids, 5,7-dihydroxy-2',4'-dimethoxy-5'-(3-methylbut-2-enyl) isoflavanone (erycaffra A) (1), 5,7-dihydroxy-2',4'-dimethoxy-5'-(2-hydroxy-3-methylbut-3-enyl)isoflavanone (erycaffra B) (2), and 5,7-dihydroxy-6,8-di-(2-hydroxy-3-methylbut-3-enyl)isoflavone (erycaffra C) (3), were isolated from the stem bark of E. caffra Thunb., along with eight known compounds, namely, alpinumisoflavone (4), isoerysenegalensein E (5), beta-amyrin (6), oleanolic acid (7), octacosyl-E-ferulate (8), triacontyl-4-hydroxycinnamate (9), n-tetracosyl p-coumarate (10) and octacosan-1-ol (11). The structures were determined on the basis of spectroscopic (1D, 2D-NMR) and MS data and by comparison with literature values.

New flavonoids from the stem bark of Erythrina caffra Thunb.

Three new flavonoids 5,7-dihydroxy-2',4'-dimethoxy-5'-formylisoflavanone (erycaffra E) (1), 5,7-dihydroxy-3'-(2″-hydroxy-3″-methylbut-3-enyl)-5'-(3‴-hydroxy-3‴-methyl-trans-but-1-enyl)-4'-methoxyflavanone (erycaffra D) (2) and 5,7-dihydroxy-4'-methoxy-3',5'-di-(3″-hydroxy-3″-methyl-trans-but-1-enyl)flavanone (erycaffra F) (3) were isolated from the stem bark of Erythrina caffra along with four known compounds, namely 5,4'-dihydroxy-6-(3″-methylbut-2″-enyl)-5‴-hydroxyisopropyldihydrofurano[2‴,3‴:7,8]isoflavone (isosenegalensein) (4), 5,7-dihydroxy-4'-methoxy-3'-(3″-methylbut-2-enyl)-5'-(3‴-hydroxy-3‴-methylbut-1-enyl)flavanone (burttinone) (5), 5,4'-dihydroxy-5″-hydroxyisopropyldihydrofurano[2‴,3‴:7,6]isoflavone (erythrinin C) (6) and 5,4'-dihydroxy-6″-hydroxymethyl-6″-methylpyrano[2″,3″:6,7]isoflavone (erysubin B) (7). The structures were determined on the basis of spectroscopic data (1D, 2D NMR and MS) and by comparison with literature values.

Assessment of free-radical scavenging activity of Gypsophila pilulifera: assay-guided isolation of verbascoside as the main active component

Gypsophila pilulifera, Boiss & Heldr, Caryophyllaceae, is a perennial medicinal herb that grows in the southwestern region of Turkey. Except for only one report on the isolation of cytotoxic saponins from the underground parts of G. pilulifera, there are no published thorough phytochemical or bioactivity studies on this species. In the present study, the free-radical scavenging activity of extracts and fractions of the stems of G. pilulifera was evaluated, using a slightly modified and more precise version of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reported here for the first time. The DPPH assay-guided HPLC-PDA-purification of the active solid-phase extraction fraction (50% methanol in water) of the methanolic extract exhibited verbascoside as the main free-radical scavenger present in this species. The structure of this active compound was resolved by spectroscopy, and the free-radical scavenging potential of verbascoside was determined.

Polyphenols: a diverse class of multi-target anti-HIV-1 agents.

Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti- HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols - according to their respective compound classes - exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process.

Extraction and isolation of saponins.

Due to their special structural features, extraction and isolation of saponins poses a serious challenge. Conventional methods have been explored as well as the recent, relatively greener, efficient, solvent-economic, time-saving, newer methods of extraction. Both traditional and recent methods of isolation are also discussed. Finally, examples are given involving both conventional and newer methods of extraction and isolation. Though in general it is difficult to use a single technique for isolation of saponins, recent literature work seems to point to the fact that high speed counter-current separation coupled to evaporative light scattering detector (ELSD) gives superior separation. The ELSD appears to have circumvented the long-standing problem of saponin detection as most of these do not have a chromophore, and hence making UV detection only nonspecific and at range 200-210 nm.

A flavanone and antimicrobial activities of the constituents of extracts from Mundulea sericea.

In this study, 12 compounds, which include a new flavanone 5-methoxy mundulin, were isolated from the leaves, stem bark and twigs of Mundulea sericea (Willd.) A. Chev. (Fabaceae; Papilionoideae). The structures of the compounds were identified based on spectral data analyses. The constituents of M. sericea also showed antimicrobial activities (MIQ = 0.01-100 µg) against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans.

Tylosema esculentum extractives and their bioactivity.

The investigation of Tylosema esculentum (Morama) husks, cotyledons, and tuber yielded griffonilide 2, compound 1, griffonin 3, gallic acid 4, protocatechuic acid 5, ß-sitosterol 6, behenic acid 7, oleic acid 8, sucrose 9, 2-O-ethyl-α-D-glucopyranoside 10, kaempferol 11 and kaempferol-3-O-ß-D-glucopyranoside 12. The structures of the isolates were determined by NMR, HR-TOF EIMS, IR and UV-vis spectroscopy, and by comparison with literature data. The husk EtOAc and n-butanol extracts demonstrated >90% DPPH radical scavenging activity at concentrations of 25, 50 and 250 µg/mL. Furthermore the husk extracts showed higher total phenolic content (233 mg GAE/g). The extractives exhibited minimum inhibitory quantities of 50-100 µg or no activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans. The tuber extracts were inactive against Caco-2 and Hela cell lines, while the husk extracts showed low activity against Caco-2 and Vero cell line with IC(50) values >400 µg/mL. The GC-MS analysis showed the beans and tuber non-polar (n-hexane) extracts major constituents as fatty acids.

Dihydro-beta-agarofuran sesquiterpenes and pentacyclic triterpenoids from the root bark of Osyris lanceolata.

Three new dihydro-beta-agarofuran polyesters, 1alpha,9beta-difuranoyloxy-2-oxodihydro-beta-agarofuran (1), 1alpha,9beta-difuranoyloxy-2-oxo-3-enedihydro-beta-agarofuran (2), and 1alpha,9beta-difuranoyloxydihydro-beta-agarofuran (3), have been isolated from the CHCl(3) extract of the root bark of Osyris lanceolata, together with two known pentacylic triterpenoids, 4 and 5. Compounds 1-5 did not scavenge the DPPH radical within 30 min of reaction time. All five compounds displayed antifungal activity against Candida albicans. Compounds 1, 3, 4, and 5 showed antibacterial activity against the Gram-positive Bacillus subtilis and Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa, with 4 and 5 being the most active. Compound 2 displayed weak antibacterial activity only against Escherichia coli.

Radical scavenging activity and total phenolic content of extracts of the root bark of Osyris lanceolata.

The root bark of Osyris lanceolata was screened for its antioxidant potential using three variations of the DPPH radical scavenging method viz a TLC-autographic assay, a semi-quantitative TLC assay, and a spectrophotometric assay. The total phenolic content was evaluated as gallic acid equivalents (GAE) using the Folin-Ciocalteu method. The powdered root bark was extracted sequentially with n-hexane, chloroform, methanol and 90% methanol/water. A separate supercritical fluid extraction (SFE) of the root bark was also carried out. The radical scavenging ability, as measured by IC50 values, was found to be 48.4 +/- 0.4 and 49.5 +/- 1.9 microg/mL for the 90% methanol/water and methanol extracts respectively, while those of the chloroform, n-hexane, and SFE extracts were found to be > 250 microg/mL. Under the same conditions, the values for the standards, ascorbic acid and gallic acid, were found to be 38.70 +/- 0.08 and 2.86 +/- 0.01 microg/mL respectively. The radical scavenging power of the five extracts correlated positively with the total phenolic content and was ranked in the following decreasing order: 90% methanol/water > methanol > chloroform > SFE > n-hexane with total phenolic contents of 290.2 +/- 3.3, 271.0 +/- 3.7, 74.4 +/- 0.8, 62.5 +/- 0.4 and 49.5 +/- 1.9 mg GAE/g of dry extract, respectively. The 90% methanol/water and methanol extracts showed several components with high antioxidant activity displaying fast kinetics in both TLC assays, while the chloroform, SFE, and n-hexane extracts exhibited slow kinetics antioxidant activity.

Antioxidant phenolic compounds from the leaves of Erica Arborea (Ericaceae).

Reversed-phase HPLC analyses of the methanol extract of the leaves of Erica arborea afforded a novel phenylpropanoid glucoside, named ericarborin, together with five flavonoids, dihydromyricetin 3-O-alpha-L-rhamnopyranoside, quercetin 3-O-beta-D-glucopyranoside, quercetin 3-O-alpha-L-rhamnopyranoside, apigenin 7-O-beta-D-glucopyranoside and apigenin 7-O-beta-D-(6-O-acetyl-glucopyranoside). While the structure of ericarborin was determined by extensive 1D and 2D NMR analyses, the structures of all known flavonoids were determined by direct comparison of their spectroscopic data with respective literature data. The antioxidant properties of these compounds were assessed by the DPPH assay. The chemotaxonomic significance of these phenolic compounds has been discussed.

Constituents of Gardenia volkensii: their brine shrimp lethality and DPPH radical scavenging properties.

The seeds and the pulp of Gardenia volkensii yielded one new iridiod, namely 4-(2N-gardenamide)n-butanoic acid, together with the known iridoids genipin and genipin gentiobioside, the pterocarpin medicarpin, coumarins, phenylpropanoids, benzenoids and triterpenes. The structures of these were determined on the basis of spectroscopic data and by comparison of obtained data with those from literature. The fruit extracts of this plant exhibited moderate radical scavenging activity against DPPH radical and moderate lethality against brine shrimps (Artemia salina).

Eremostachiin: a new furanolabdane diterpene glycoside from Eremostachys glabra.

The reversed-phase preparative HPLC analysis of the methanol extract of the rhizomes of Eremostachys glabra (Lamiaceae) led to the isolation of two furanolabdane diterpene glycosides, phlomisoside II, and beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid (named eremostachiin), the latter being a novel natural product. The structure of the new compound has been elucidated unambiguously by HRMS and a series of 1D- and 2D-NMR spectroscopic techniques. The free radical scavenging activity of these compounds was assessed using the DPPH assay.

Antimicrobial and radical scavenging flavonoids from the stem wood of Erythrina latissima.

From the stem wood of Erythrina latissima, two isoflavones and a flavanone were isolated and characterized as 7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)isoflavone (erylatissin A), 7,3'-dihydroxy-6'',6''-dimethyl-4'',5''-dehydropyrano [2'',3'': 4',5']isoflavone (erylatissin B), (-)-7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)flavanone (erylatissin C), respectively, in addition to 10 known flavonoids. Structures of these compounds were determined on the basis of their spectroscopic data. These compounds showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Candida mycoderma. The isolated compounds also exhibited weak radical scavenging properties towards DPPH radical.

Erythrinaline alkaloids from the flowers and pods of Erythrina lysistemon and their DPPH radical scavenging properties.

Fourteen different erythrinaline alkaloids have been isolated from the flowers and pods of Erythrina lysistemon with four being reported for the first time in nature and five for the first time in this species and the rest having been re-isolated. The new compounds are (+)-11beta-hydroxyerysotramidine (1), (+)-11beta-methoxyerysotramidine (2), (+)-11beta-hydroxyerysotrine N-oxide (4) and (+)-11beta-hydroxyerysotrine (8). (+)-11alpha-Hydroxyerysotrine N-oxide (3), earlier misidentified as erythrartine N-oxide (beta-hydroxyerysotrine N-oxide 4), was also re-isolated along with four other alkaloids. Correct identification of compounds 4 and 8 was aided by the fact that the two sets of C-11 epimers 3, 4 and 8, 9 were both isolated in this study thus making it easier to identify and assign the individual epimers. (+)-Erythristemine (14) was found distributed in most of the plant parts investigated. Preliminary work on the crude chloroform/methanol (1:1) showed moderate toxicity to brine shrimp (LC50 23 ppm) and moderate (IC50 86 microg/ml) radical scavenging properties against stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The DPPH radical scavenging properties of the isolated compounds were assessed using TLC autographic and spectrophotometric assays whereupon only compounds 11 (1 microg; 90 microg/ml) and 12 (0.1 microg; 160 microg/ml) showed any notable activity. It appears the two compounds are slow reacting and do not reach steady state conditions within the standard half an hour time frame but only seemed to have reached steady state conditions after 4 h.