Antimicrobial activity of kaurane diterpenes against oral pathogens

Two kaurane diterpenes, ent-kaur-16(17)-en-19-oic acid (KA) and 15-beta-isovaleryloxy-ent-kaur-16(17)-en-19-oic acid (KA-Ival), isolated from Aspilia foliacea, and the methyl ester derivative of KA (KA-Me) were evaluated against oral pathogens. KA was the most active compound, with MIC values of 10 microg mL(-1) against the following microorganisms: Streptococcus sobrinus, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Lactobacillus casei. However, KA did not show significant activity against Streptococcus salivarius and Enterococcus faecalis, with MIC values equal to 100 and 200 microg mL(-1), respectively. Our results show that KA has potential to be used as a prototype for the discovery of new effective anti-infection agents against microorganisms responsible for caries and periodontal diseases. Moreover, these results allow to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to studies on the structure-activity relationship of this type of metabolites with respect to caries and periodontal diseases.     

Antibacterial serrulatane diterpenes from the Australian native plant Eremophila microtheca

Chemical investigations of the aerial parts of the Australian plant Eremophila microtheca resulted in the isolation of three serrulatane diterpenoids, 3-acetoxy-7,8-dihydroxyserrulat-14-en-19-oic acid (1), 3,7,8-trihydroxyserrulat-14-en-19-oic acid (2) and 3,19-diacetoxy-8-hydroxyserrulat-14-ene (3) as well as the previously reported compounds verbascoside (4) and jaceosidin (5). Acetylation and methylation of the major serrulatane diterpenoid 2 afforded 3,8-diacetoxy-7-hydroxyserrulat-14-en-19-oic acid (6) and 3,7,8-trihydroxyserrulat-14-en-19-oic acid methyl ester (7), respectively. The antibacterial activity of 1–7 was assessed against a panel of Gram-positive and Gram-negative bacterial isolates. All of the serrulatane compounds exhibited moderate activity against Streptococcus pyogenes (ATCC 12344) with minimum inhibitory concentrations (MICs) ranging from 64–128 μg/mL. Serrulatane 1 demonstrated activity against all Gram-positive bacterial strains (MICs 64–128 μg/mL) except for Enterococcus faecalis and Enterococcus faecium. This is the first report of natural products from E. microtheca.     

Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (?)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain.     

Terpenes with antimicrobial activity from Cretan propolis

Five terpenes, the diterpenes: 14,15-dinor-13-oxo-8(17)-labden-19-oic acid and a mixture of labda-8(17),13E-dien-19-carboxy-15-yl oleate and palmitate as well as the triterpenes, 3,4-seco-cycloart-12-hydroxy-4(28),24-dien-3-oic acid and cycloart-3,7-dihydroxy-24-en-28-oic acid were isolated from Cretan propolis. Moreover, 18 known compounds were also isolated, seven of them for the first time as propolis components. All structures were established on the basis of spectroscopic analysis and chemical evidence. All isolated compounds were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria as well as against some human pathogenic fungi showing a broad spectrum of antimicrobial activity.     

Triterpenoid saponins from Pteleopsis suberosa stem bark

Thirteen oleanane saponins (1-13), four of which were new compounds (1-4), were isolated from Pteleopsis suberosa Engl. et Diels stem bark (Combretaceae). Their structures were determined by 1D and 2D NMR spectroscopy and ESI-MS spectrometry. The compounds were identified as 2alpha,3beta,19alpha,23,24-pentahydroxy-11-oxo-olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester (1), 2alpha,3beta,19beta,23,24-pentahydroxy-11-oxo-olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester (2), 2alpha,3beta,19alpha,23-tetrahydroxy-11-oxo-olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester (3), and 2alpha,3beta,6beta,19alpha,24-pentahydroxy-11-oxo-olean-12- en-28-oic acid 28-O-beta-D-glucopyranosyl ester (4). The presence of alpha,beta-unsaturated carbonyl function was not common in the oleanane class and the aglycons of these compounds were not found previously in the literature. Moreover, the isolated compounds were tested against Helicobacter pylori standard and vacA, and cagA clinical virulence genotypes. Results showed that compound 6 has an anti-H. pylori activity against three metronidazole-resistant strains (Ci 1 cagA, Ci 2 vacA, and Ci 3).     

Biotransformation using <Emphasis Type="Italic">Mucor rouxii</Emphasis> for the production of oleanolic acid derivatives and their antimicrobial activity against oral pathogens

The goal of this study is to produce oleanolic acid derivatives by biotransformation process using Mucor rouxii and evaluate their antimicrobial activity against oral pathogens. The microbial transformation was carried out in shake flasks at 30°C for 216 h with shaking at 120 rpm. Three new derivatives, 7β-hydroxy-3-oxo-olean-12-en-28-oic acid, 7β,21β-dihydroxy-3-oxo-olean-12-en-28-oic acid, and 3β,7β,21β-trihydroxyolean-12-en-28-oic acid, and one know compound, 21β-hydroxy-3-oxo-olean-12-en-28-oic acid, were isolated, and the structures were elucidated on the basis of spectroscopic analyses. The antimicrobial activity of the substrate and its transformed products was evaluated against five oral pathogens. Among these compounds, the derivative 21β-hydroxy-3-oxo-olean-12-en-28-oic acid displayed the strongest activity against Porphyromonas gingivalis, which is a primary etiological agent of periodontal disease. In an attempt to improve the antimicrobial activity of the derivative 21β-hydroxy-3-oxo-olean-12-en-28-oic acid, its sodium salt was prepared, and the minimum inhibitory concentration against P. gingivalis was reduced by one-half. The biotransformation process using M. rouxii has potential to be applied to the production of oleanolic acid derivatives. Research and antimicrobial activity evaluation of new oleanolic acid derivatives may provide an important contribution to the discovery of new adjunct agents for treatment of dental diseases such as dental caries, gingivitis, and periodontitis.     

Isolation of anti-Candida albicans compounds from Markhamia obtusifolia (Baker) Sprague (Bignoniaceae)

An increase in clinical cases of Candidiosis globally as well as fungal resistance to drugs prompted the search for novel anti-Candida albicans agents from plant sources. Leaf extracts of Markhamia obtusifolia were screened for activity against C. albicans in vitro. An acetone extract obtained following serial exhaustive extraction contained mainly the active components with at least four active zones on the bioautogram. Bioassay guided fractionation of this extract led to the isolation of three compounds which inhibited the growth of three C. albicans strains. Based on spectroscopy studies (NMR and MS), the compounds were identified as 3β-hydroxyurs-12-en-28-oic acid, ursolic acid (1) 3β, 19α-dihydroxyurs-12-en-28-oic acid, pomolic acid (2) and 2β, 3β, 19α -trihydroxy-urs-12-en-28-oic acid, 2-epi-tormentic acid (3). The most active compound was 3β, 19α-dihydroxy-12-ursen-28-oic acid (2) with a minimum inhibitory concentration (MIC) value of 12.5 µg/mL for C. albicans isolated from dog and 25.0 µg/mL for C. albicans from cat and ATCC 90028 at 24 h following incubation. However, at 48 h of incubation MICs were > 400 µg/mL for all the three compounds isolated. This study indicated that M. obtusifolia could be a potential source of active principles against C. albicans.     

ent-Kaurenoic acids from Mikania hirsutissima (Compositae)

Four ent-kaurenoic acid derivatives, 2beta,16alpha,17-trihydroxy-ent-kauran-19-oic acid (1), 3beta,16alpha,17-trihydroxy-ent-kauran-19-oic acid (2), 11alpha,15beta-dihydroxy-7-O-beta-d-glucopyranosyl-ent-kaur-16-en-19-oic acid (3) and 1alpha,15beta-dihydroxy-7-O-beta-d-glucopyranosyl-ent-kaur-16-en-19-oic acid (4), were isolated together with five known compounds, 1,5-dicaffeoyl-quinic acid (5), 2-O-glucosyloxy-4-methoxy-cinnamic acid (6), phenethyl alcohol glucoside (7), phenethyl-1-O-beta-d-apiofuranosyl (1-->2) beta-d-glucopyranoside (sayaendoside) (8) and 3,6-dihydroxy-beta-ion-9-ol (9) from the 50% aqueous acetone extract of the aerial parts of Mikania hirsutissima DC. (Compositae). Compounds 1-9 were tested for their proliferative activity toward peripheral blood mononuclear cells (hPBMC); compounds 1 and 2 showed significant activity (43.8% and 36.7%, at 100 microM, respectively) on the lymphocyte.     

Plant growth regulation activity of steviol and derivatives

This work describes the preparation of tetracyclic diterpenoids and determination of their plant growth regulator properties. Stevioside (2) was used as starting material and the derivatives 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol, 3), ent-7alpha,13-dihydroxy-kaur-16-en-19-oic acid (4), 13-hydroxy, ent-kaur-16,17-epoxi-19-oic acid (steviol epoxide, 5), 17-hydroxy-16-ketobayeran-19-oic acid (17-hydroxyisosteviol, 6), 17-hydroxy-16-hydroxyiminobayeran-19-oic acid (7), 16-ketobayeran-19-oic acid (isosteviol, 9), 16,17-dihydroxybeyeran-19-oic acid (8), and 16-hydroxyiminobayeran-19-oic acid (isosteviol oxime, 10) were obtained by simple chemical procedures. Another derivative, ent-7alpha,13-dihydroxycaur-15-en-19-oic acid (4), was obtained by biotransformation of steviol (3) by Penicillium citrinum. In order to determine the plant growth regulator activity the compounds were submitted to the lettuce hypocotyl and barley aleurone bioassays. All compounds showed significant activities in both bioassays. Steviol (3) and isosteviol (9) were also tested in field-grown grapes resulting in an increase in berry weight and size.     

Insect-antifeedant and antibacterial activity of diterpenoids from species of Plectranthus

Bio-assay guided fractionation of an acetone extract of leaf material from Plectranthus saccatus Benth. resulted in the isolation of a beyerane diterpenoid. This compound, characterised by spectroscopic methods as ent-3beta-(3-methyl-2-butenoyl)oxy-15-beyeren-19-oic acid, showed insect antifeedant activity against Spodoptera littoralis. Known quinonoid abietane diterpenoids obtained from new sources included a mixture of the (4R,19R) and (4R,19S) diastereoisomers of coleon A from P. aff. puberulentus J.K. Morton, coleon A lactone from P. puberulentus J.K. Morton, and coleon U and coleon U quinone from P. forsteri 'Marginatus' Benth. These compounds, and the crude acetone extracts from the leaf surfaces of 11 species of Plectranthus, were tested for antifeedant activity against S. littoralis, antibacterial activity against Bacillus subtilis and Pseudomonas syringae and antifungal activity against Cladosporium herbarum. The coleon A mixture showed potent antifeedant activity against S. littoralis, whereas coleon U showed the greatest antimicrobial activity.     

New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae)

Fractionation of a MeOH/CH₂Cl₂ (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16α,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7β-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-β-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism.     

Microbial metabolism of steviol and steviol-16alpha,17-epoxide

Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7alpha,11beta,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7alpha,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-alpha-d-glucopyranosyl ester (4), ent-13,16beta,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16alpha,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (10), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16beta-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11beta,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (12), and ent-11beta,13,16beta,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.     

Constituents of various wood-rotting basidiomycetes

Phytochemical investigation of n-hexane and methanol extracts of fruiting bodies of the wood-rotting fungi Fomitopsis pinicola. Ganoderma lipsiense, Fomes fomentarius and Gloeophyllum odoratum led to the isolation and identification of several triterpene derivatives and some aromatic compounds derived from lignin. These are the new natural products, namely, pinicolic acid E (16alpha-hydroxy-3-oxolanosta-8,24-dien-21-oic acid) and pinicolol C (3-oxolanosta-7,9(11),24-trien-15alpha,21-diol) from the crust of F. pinicola, ganoderenic acid D [(E)-7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20(22)-di en-26-oic acid] and ganoderic acid N (7beta,20-dihydroxy-3,11,15,23-tetraoxolanost-8-en-26-oic acid) from G. lipsiense and ergosterol peroxide (5alpha,8alpha-epi-dioxyergost-6-en-3beta-ol) as well as ergost-7-en-3-one from F. fomentarius. From G. odoratum, dehydroeburicoic acid [24-methylene-3-oxolanosta-7,9(11)-dien-21-oic acid], the dimethylacetal of 4,4,14alpha-trimethyl-24-oxo-5alpha-chol-8-en-21-oic acid and some aromatic compounds, of which 1-(4'-methoxyphenyl)-1,2-ethandiol is a new natural product, were isolated. Furthermore, a complete set of 13C NMR data of the steryl esters 3beta-linoleyloxyergosta-7,24(28)-diene, 3beta-linoleyloxyergosta-7,24-diene and 3beta-linoleyloxyergost-7-ene, which could be identified as a mixture in all investigated fungi, could be recorded. It was proved by HPLC and TLC investigations, that the crust on top of the fruiting bodies of F. pinicola consists of lanostane derivatives.     

Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds

A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds 1 and 2, respectively, to aid in their structure elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are isolated for the first time from the seeds of P. kurroa.     

Cytotoxic triterpenoids from the root bark of Helicteres angustifolia

Three new triterpenoids, 3beta-acetoxy-27-[(E)-cinnamoyloxy]lup-20(29)-en-28-oic acid methyl ester (1), 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]lup-20(29)-en-28-oic acid (2), and 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester (3), together with nine known triterpenoids, 4-12, were isolated from the root bark of Helicteres angustifolia. The structures of these compounds were established on the basis of spectroscopic methods including 2D-NMR experiments. All twelve compounds were tested for their cytotoxic activities against human colorectal cancer (COLO 205), human hepatoma (Hep G2), and human gastric cancer (AGS) cell lines in vitro. Among them, compounds 2, 3, 3beta-O-[(E)-coumaroyl]betulinic acid (6), and pyracrenic acid (7) showed significant cytotoxic activities against human cancer cells COLO 205 and AGS.     

Isolation and absolute configuration of new bioactive marine steroids from Euryspongia n. sp

The apolar fraction of the crude alcoholic extract of the sponge Euryspongia n. sp. was shown to display anti-inflammatory activity. Bioassay guided chromatographic purification led to the isolation of a known compound petrosterol (1) of 3beta-hydroxy-24-norchol-5-en-23-oic acid (2), which has never yet been found as a natural substance, and of a new steroid, 3beta-hydroxy-26-norcampest-5-en-25-oic acid (3). The absolute configurations of 2 and 3 were deduced from comparative 1H NMR data of the (S)- and (R)-phenylglycine methyl ester derivatives. These compounds were evaluated for their anti-inflammatory activity against 6-keto-prostaglandinF1alpha release in a human keratinocyte cell line HaCaT.     

Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (Celastraceae)

Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial, antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively, while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested.     

Antimalarial constituents from Nauclea orientalis (L.) L

Bioassay-guided fractionation of the antimalarial-active CHCl3 extract of the dried stem of Nauclea orientalis (L.) L. (Rubiaceae) has resulted in the isolation of two novel tetrahydro-beta-carboline monoterpene alkaloid glucosides, naucleaorine (= (16alpha,17beta)-3,14:15,20-tetradehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)-19alpha-methoxyoxayohimban-21-one; 1) and epimethoxynaucleaorine (2), as well as the known compounds, strictosidine lactam (= (15beta,16alpha,17beta)-19,20-didehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)oxayohimban-21-one; 3), 3,4,5-trimethoxyphenol (4), 3alpha-hydroxyurs-12-en-28-oic acid methyl ester (5), 3alpha,23-dihydroxyurs-12-en-28-oic acid (6), 3alpha,19alpha,23-trihydroxyurs-12-en-28-oic acid methyl ester (7), and oleanolic acid (8). Compounds 1, 2, 6, and 8 showed moderate in vitro activities against Plasmodium falciparum. Their structures and configurations were elucidated by spectroscopic methods including 1D- and 2D-NMR analyses.     

Triterpenoids from Sanguisorba officinalis

Seven triterpenoids, i.e., 3beta-[(alpha-L-arabinopyranosyl)oxy]-19beta-hydroxyurs-12,20(30)-dien-28-oic acid (1), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-11,13(18)-dien-28-oic acid beta-D-glucopyranosyl ester (2), 2alpha,3alpha,23-trihydroxyurs-12-en-24,28-dioic acid 28-beta-D-glucopyranosyl ester (3), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(20)-dien-28-oic acid (4), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(29)-dien-28-oic acid (5), 3beta-[(alpha-L-arabinopyranosyl)oxy]-19alpha-hydroxyolean-12-en-28-oic acid (6), 2alpha,3beta-dihydroxy-28-norurs-12,17,19(20),21-tetraen-23-oic cid (7), together with three known ones (8-10), were isolated from the roots of Sanguisorba officinalis. Their structures were determined by spectroscopic and chemical methods. Compounds 7 and 10 showed marginal inhibition activity against the growth of tumor cell lines.     

Triterpene saponins from Chenopodium quinoa Willd

Twenty triterpene saponins (1-20) have been isolated from different parts of Chenopodium quinoa (flowers, fruits, seed coats, and seeds) and their structures have been elucidated by analysis of chemical and spectroscopic data including 1D- and 2D-NMR. Four compounds (1-4) were identified: 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-23-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (1), 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-27-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (2), 3-O-alpha-l-arabinopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (3), and 3-O-beta-d-glucuronopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (4). The following known compounds have not previously been reported as saponin constituents from the flowers and the fruits of this plant: two bidesmosides of serjanic acid (5,6), four bidesmosides of oleanolic acid (7-10), five bidesmosides of phytolaccagenic acid (11-15), four bidesmosides of hederagenin (16-19), and one bidesmoside of 3beta,23,30-trihydroxy olean-12-en-28-oic acid (20). The cytotoxicity of these saponins and their aglycones was tested in HeLa cells. Induction of apoptosis in Caco-2 cells by bidesmosidic saponins 1-4 and their aglycones I-III was determined by flow cytometric DNA analysis. The saponins with an aldehyde group were most active. The relationships between structure and cytotoxic activity of saponins and their aglycones are discussed.