RESUMO
A bioassay-guided fractionation of Juniperus procera berries yielded antiparasitic, nematicidal and antifouling constituents, including a wide range of known abietane, pimarane and labdane diterpenes. Among these, abieta-7,13-diene (1) demonstrated in vitro antimalarial activity against Plasmodium falciparum D6 and W2 strains (IC(50) = 1.9 and 2.0 microg/mL, respectively), while totarol (6), ferruginol (7) and 7beta-hydroxyabieta-8,13-diene-11,12-dione (8) inhibited Leishmania donovani promastigotes with IC(50) values of 3.5-4.6 microg/mL. In addition, totarol demonstrated nematicidal and antifouling activities against Caenorhabditis elegans and Artemia salina at a concentration of 80 microg/mL and 1 microg/mL, respectively. The resinous exudate of J. virginiana afforded known antibacterial E-communic acid (4) and 4-epi-abietic acid (5), while the volatile oil from its trunk wood revealed large quantities of cedrol (9). Using GC/MS, the two known abietanes totarol (6) and ferruginol (7) were identified from the berries of J. procera, J. excelsa and J. phoenicea.
Assuntos
Abietanos/farmacologia , Antinematódeos/farmacologia , Antiprotozoários/farmacologia , Diterpenos/farmacologia , Juniperus/química , Animais , Antibacterianos/farmacologia , Artemia/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Leishmania donovani/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Plasmodium falciparum/efeitos dos fármacos , Resinas Vegetais/químicaRESUMO
Morinda citrifolia L. (Rubiaceae), known as noni, has a long history of traditional use in the Hawaiian and Tahitian islands. More recently, an array of commercial noni fruit juice products are gaining popularity as dietary supplements, with claims of anticancer and immunostimulant activities. The biologically active principles of noni are not fully known. In continuation of work on the isolation of markers from dietary supplements, this paper reports the isolation of three new markers, namely, 1-O-(3'-methylbut-3'-enyl)-beta-D-glucopyranose (1), 1-n-butyl-4-(5'-formyl-2'-furanyl)methyl succinate (2), and 4-epi-borreriagenin (3), together with the known iridoid glycosides asperulosidic acid (4) and deacetylasperulosidic acid (5) and a mixture of 1-n-butyl-4-methyl-2-hydroxysuccinate (6a) and 1-n-butyl-4-methyl-3-hydroxysuccinate (6b), as well as a mixture of alpha- and beta-glucopyranose from noni fruit juice obtained from Puerto Rico. The structures of compounds were based on 1H and 13C NMR, mainly 2D NMR COSY, HMQC, HMBC, and NOESY experiments, and HRMS. Furthermore, samples from fresh-squeezed noni fruit juice from Japan revealed the presence of scopoletin (7), in addition to compounds 1-6, indicating no significant differences in the marker constituents of noni collected from Atlantic and Pacific regions.
Assuntos
Bebidas/análise , Frutas/química , Morinda/química , Cromatografia em Camada Fina , Glicosídeos/análise , Espectroscopia de Ressonância MagnéticaRESUMO
Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC(50) values 0.2, 1.1, and 0.11 muM, respectively). Compounds 1, 2, and 4 inhibited both hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1alpha protein accumulation.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Proteínas de Ligação a DNA/efeitos dos fármacos , Emetina/química , Emetina/farmacologia , Proteínas Nucleares/efeitos dos fármacos , Quinazolinas/química , Quinazolinas/farmacologia , Terpenos/química , Terpenos/farmacologia , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/farmacologia , Fatores de Transcrição/efeitos dos fármacos , Neoplasias da Mama , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Estrutura Molecular , Rubiaceae/química , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
Maca (Lepidium meyenii) has been used as a food in Peru for thousands of years. More recently a wide array of commercial maca products have gained popularity as dietary supplements, with claims of anabolic and aphrodisiac effects, although the biologically active principles are not fully known. In an earlier chemical investigation, two new alkamides and a novel fatty acid, as well as the N-hydroxypyridine derivative, macaridine, were isolated from L. meyenii. Further examination has led to the isolation of five additional new alkamides, namely, N-benzyl-9-oxo-12Z-octadecenamide (1), N-benzyl-9-oxo-12Z,15Z-octadecadienamide (2), N-benzyl-13-oxo-9E,11E-octadecadienamide (3), N-benzyl-15Z-tetracosenamide (4), and N-(m-methoxybenzyl)hexadecanamide (5). Their structures were established by spectrometric and spectroscopic methods including ESI-HRMS, EI-MS, (1)H, (13)C, and 2D NMR, as well as (1)H-(15)N 2D HMBC experiments. In addition, the identity of N-benzyl-15Z-tetracosenamide (4) was confirmed by synthesis. These compounds have been found from only L. meyenii and could be used as markers for authentication and standardization.
Assuntos
Amidas/análise , Lepidium/química , Tubérculos/química , Amidas/química , Amidas/isolamento & purificação , Ácidos Graxos/análise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Piridinas/análise , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Psychotria klugii yielded two new benzoquinolizidine alkaloids, klugine (1) and 7'-O-demethylisocephaeline (2), together with the previously known cephaeline (3), isocephaeline (4), and 7-O-methylipecoside (5). The structures and stereochemistry of 1 and 2 were determined by 1D and 2D NMR data and circular dichroism experiments. Cephaeline (3) demonstrated potent in vitro antileishmanial activity against Leishmania donavani (IC(50) 0.03 microg/mL) and was >20- and >5-fold more potent than pentamidine and amphotericin B, respectively, while klugine (1) (IC(50) 0.40 microg/mL) and isocephaeline (4) (IC(50) 0.45 microg/mL) were <13- and <15-fold less potent than 3. In addition, emetine (6) (IC(50) 0.03 microg/mL) was found to be as equally potent as 3, but was >12-fold more toxic than 3 against VERO cells (IC(50) 0.42 vs 5.3 microg/mL). Alkaloids 1 and 3 exhibited potent antimalarial activity against Plasmodium falciparum clones W2 and D6 (IC(50) 27.7-46.3 ng/mL). Compound 3 was cytotoxic to SK-MEL, KB, BT-549, and SK-OV-3 human cancer cells, while 1 was inactive.
Assuntos
Alcaloides , Antimaláricos , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Psychotria/química , Quinazolinas/isolamento & purificação , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Leishmania donovani/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peru , Quinazolinas/química , Quinazolinas/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (HHDBP's), machaeriol C (1) and machaeriol D (2), and three new 5,6-seco-HHDBP's, machaeridiol A (3), machaeridiol B (4), and machaeridiol C (5). Their structures and stereochemistries were determined by 1D and 2D NMR data, including HMBC, NOESY, and circular dichroism experiments. Machaeriol C (1) demonstrated in vitro antibacterial activity against Staphylococcus aureus (IC(50) 0.65 microg/mL) and methicillin-resistant S. aureus (MRSA) (IC(50) 0.70 microg/mL), while its corresponding 5,6-seco-analogues machaeridiol A (3) and machaeridiol B (4) showed antibacterial activity against S. aureus and MRSA (IC(50) 1.0-2.6 microg/mL) and antifungal activity against Candida albicans (IC(50), 2.0-3.5 microg/mL). In addition, machaeridiol B (4) demonstrated antiparasitic activities against Plasmodium falciparum D6 and W2 clones and Leishmania donavani with IC(50) values of 0.64, 0.22, and 0.9 microg/mL, respectively.
Assuntos
Anti-Infecciosos/isolamento & purificação , Antimaláricos/isolamento & purificação , Antiparasitários/isolamento & purificação , Benzopiranos/isolamento & purificação , Fabaceae/química , Plantas Medicinais/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Candida albicans/efeitos dos fármacos , Concentração Inibidora 50 , Leishmania donovani/efeitos dos fármacos , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peru , Casca de Planta/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , EstereoisomerismoRESUMO
In addition to the previously reported (+)-araguspongine A, (+)-araguspongine C, (+)-araguspongine D, (-)-araguspongine E, and (+)-xestospongin B, two new N-oxide araguspongines, (+)-araguspongine K and (+)-araguspongine L, are described here. Their structures were established on the basis of spectral analyses including (1)H-(15)N HMBC. The promising in vitro antimalarial and antituberculosis activities of araguspongine C are reported.
Assuntos
Alcaloides/isolamento & purificação , Antimaláricos/isolamento & purificação , Antituberculosos/isolamento & purificação , Poríferos/química , Quinolizinas/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Antituberculosos/química , Antituberculosos/farmacologia , Oceano Índico , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Plasmodium falciparum/efeitos dos fármacos , Quinolizinas/química , Quinolizinas/farmacologia , Rifampina/farmacologia , EstereoisomerismoRESUMO
Preparative-scale fermentation of rubijervine (1), the known 22,26-epiminocholestane Veratrum alkaloid, with Cunninghamella echinulata ATCC 9244 has resulted in the isolation of the new metabolites 7alpha-hydroxyrubijervine (2) and solanid-5-ene-3beta,12alpha-diol-1-one (3). Structure elucidation of these metabolites was based primarily on 1D- and 2D-NMR analyses. The microbe C. echinulata ATCC 9244 was able to metabolize rings A and B of rubijervine but failed to metabolize rings C, D or its N-containing side chain, a finding which is analogous to the results of previous fermentation studies of steroidal alkaloids.
Assuntos
Cunninghamella/metabolismo , Alcaloides de Veratrum/química , Alcaloides de Veratrum/farmacocinética , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacocinética , Biotransformação/fisiologia , FermentaçãoRESUMO
A low-temperature structure of ginkgolide A monohydrate, (1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-4,7b-dihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione monohydrate, C(20)H(24)O(9) x H(2)O, obtained from Mo K alpha data, is a factor of three more precise than the previous room-temperature determination. A refinement of the ginkgolide A monohydrate structure with Cu K alpha data has allowed the assignment of the absolute configuration of the series of compounds. Ginkgolide C sesquihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11S,11aR)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b,11-tetrahydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione sesquihydrate, C(20)H(24)O(11) x 1.5H(2)O, has two independent diterpene molecules, both of which exhibit intramolecular hydrogen bonding between OH groups. Ginkgolide J dihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione dihydrate, C(20)H(24)O(10) x 2H(2)O, has the same basic skeleton as the other ginkgolides, with its three OH groups having the same configurations as those in ginkgolide C. The conformations of the six five-membered rings are quite similar across ginkgolides A-C and J, except for the A and F rings of ginkgolide A.
Assuntos
Diterpenos , Ginkgo biloba/química , Lactonas/química , Cristalografia por Raios X , Ginkgolídeos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
The aerial parts of Teucrium oliverianum yielded two neo-clerodane diterpenoids, teucrolin F and G, together with the known teucrolin E. The previously proposed structure for teucrolin E was revised so that it contains a tetrahydrofuran ring instead of an oxetane ring. This was based on analysis of the NMR spectroscopic data of its diacetate, including its NOE spectra. In addition, the structural assignments of the new diterpenoids were based on 1H and 13C NMR spectroscopic studies, mainly 2D NMR experiments, including homonuclear and heteronuclear correlations.
Assuntos
Diterpenos/química , Magnoliopsida/química , Diterpenos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Plantas Medicinais/químicaRESUMO
The tubers of Lepidium meyenii contain the benzylated derivative of 1,2-dihydro-N-hydroxypyridine, named macaridine, together with the benzylated alkamides (macamides), N-benzyl-5-oxo-6E,8E-octadecadienamide and N-benzylhexadecanamide, as well as the acyclic keto acid, 5-oxo-6E,8E-octadecadienoic acid. The structure elucidation of the isolated compounds was based primarily on 1D and 2D NMR spectroscopic analyses, including 1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC and 1H-1H NOESY experiments, as well as from 1H-15N NMR HMBC correlations for macaridine and N-benzylhexadecanamide.
Assuntos
Amidas/isolamento & purificação , Lepidium/química , Piridinas/isolamento & purificação , Amidas/química , Alcamidas Poli-Insaturadas , Piridinas/químicaRESUMO
In addition to the previously reported bioactive kahalalide F six new peptides are described. Six of these, including kahalalide F, are cyclic depsipeptides, ranging from a C(31) tripeptide to a C(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens. The mollusk feeds on a green alga, Bryopsis sp., which has also been shown to elaborate some of these peptides in smaller yields, in addition to an acyclic analog of F, kahalalide G. The bioassay results of antitumor, antiviral, antimalarial, and OI (activity against AIDS opportunistic infections) tests are reported.