RESUMO
CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures. Interestingly, the kinetic parameters of CsPT4 for these substrates differed depending on whether they underwent C-prenylation or O-prenylation, suggesting that this enzyme utilized different substrate-binding modes suitable for the respective reactions. Aromatic prenyltransferases that catalyze O-prenylation are rare in the plant kingdom, and CsPT4 was notable for altering the reaction specificity between C- and O-prenylations depending on the skeletons of aromatic substrates. We also demonstrated that enzymatically synthesized geranylated acylphloroglucinols had potent antiausterity activity against PANC-1 human pancreatic cancer cells, with 4'-O-geranyl THDC being the most effective. We suggest that CsPT4 is a valuable catalyst to generate biologically active C- and O-prenylated molecules that could be anticancer lead compounds.
Assuntos
Cannabis , Dimetilaliltranstransferase , Humanos , Dimetilaliltranstransferase/química , Dimetilaliltranstransferase/metabolismo , Prenilação , Catálise , Especificidade por SubstratoRESUMO
Three neo-clerodane diterpenoids, including two new tinocordifoliols A (1) and B (2) and one known tinopanoid R (3), were isolated from the ethyl acetate-soluble fraction of the 70% ethanol extract of Tinospora cordifolia stems. The structures were elucidated by various spectroscopic methods, including one dimensional (1D) and 2D-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and electronic circular dichroism (ECD) data. The T. cordifolia extract and all isolated compounds 1-3 possessed arginase I inhibitory activities. Among them, 3 exhibited moderate competitive inhibition of human arginase I (IC50 = 61.9 µM). Furthermore, docking studies revealed that the presence of a ß-substituted furan in 3 may play a key role in the arginase I inhibitory activities.
Assuntos
Arginase , Diterpenos Clerodânicos , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Caules de Planta , Tinospora , Tinospora/química , Arginase/antagonistas & inibidores , Arginase/metabolismo , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Humanos , Caules de Planta/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Relação Estrutura-Atividade , Estrutura Molecular , Conformação Molecular , Relação Dose-Resposta a DrogaRESUMO
A new phenolic derivative, galeomalate A (1), together with five known structurally related compounds (2-6), was isolated from the ethyl acetate extract of Galeola nudifolia collected in Vietnam. The structures were elucidated by various spectroscopic methods, including 1D and 2D NMR, HR-ESI-TOF-MS, and CD data, and chemical conversion of the sugar moiety. All isolated compounds possessed acetylcholinesterase (AChE) inhibitory activities in a dose-dependent manner. Among them, compounds 2 and 3 exhibited the first and second highest inhibitory activity on AChE with IC50 values of 122.13 and 125.49â µM, respectively. Compounds 1 and 4-6 inhibited the AChE activity by mixed modes of action comprising competitive and non-competitive modes, whereas 2 and 3 exerted their inhibitory activities in a competitive manner. Molecular docking analyses suggested that the phenyl-ß-D-glucopyranoside unit of 2 and 3 bound to the active site of AChE for the competitive inhibitory activities, while the mixed inhibitory activity of 4 was due to the two binding patterns in the active-site and the active-site entrance of AChE. Furthermore, the docking studies indicated that 1, 5, and 6 would inhibit AChE in a mixed inhibitory manner by adopting three distinct binding patterns of the additional phenyl-ß-D-glucopyranoside unit at the active-site entrance.
Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Vietnã , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fenóis/farmacologiaRESUMO
We investigated the importance of the δ-lactone ring (C1-C5) in lankacidin C using chemoenzymatic synthesis and computational prediction and assessing biological activity, including antitumor activity. Pyrroloquinoline quinone-dependent dehydrogenase (Orf23) in Streptomyces rochei was used in the chemoenzymatic synthesis of lankacyclinone C, a novel lankacidin C congener lacking the δ-lactone moiety. Orf23 could convert the monocyclic lankacidinol derivatives, lankacyclinol and 2-epi-lankacyclinol, to the C-24 keto compounds, lankacyclinone C and 2-epi-lankacyclinone C, respectively, elucidating the relaxed substrate specificity of Orf23. Computational prediction using molecular dynamics simulations and the molecular mechanics/generalized Born-surface area protocol indicated that binding energy values of all the monocyclic derivatives are very close to those of lankacidin C, which may reflect a comparable affinity to tubulin. Monocyclic lankacidin derivatives showed moderate antitumor activity when compared with bicyclic lankacidins, suggesting that the δ-lactone moiety is less important for antitumor activity in lankacidin-group antibiotics.
Assuntos
Antineoplásicos/farmacologia , Macrolídeos/farmacologia , Simulação de Dinâmica Molecular , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Macrolídeos/química , Macrolídeos/metabolismo , Conformação Molecular , Oxirredutases/metabolismo , Streptomyces/enzimologia , Relação Estrutura-AtividadeRESUMO
Three new flavanols, (2R,3S)-7-methoxy-flavan-3-ol (1: ), (2R,3S)-7-hydroxy-flavan-3-ol (2: ), and (2R,3S)-2'-hydroxy-7-methoxy-flavan-3-ol (3: ), together with two known flavans (4: and 5: ), were isolated from the chloroform extract of Crinum asiaticum. Their structures were elucidated by various spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, and CD data. The isolated compounds 1: and 3: -5: showed inhibitory activity toward LPS-induced nitric oxide (NO) production. Further investigation of the NF-κB pathway mechanisms indicated that 1: and 3: -5: inhibited the LPS-induced IL-6 production and p65 subunit phosphorylation of NF-κB in RAW264.7 cells, with an effective dose of 10 µM.
Assuntos
Crinum , Flavonoides/química , NF-kappa B , Animais , Crinum/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Polifenóis , Células RAW 264.7 , Transdução de SinaisRESUMO
SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol extract from Woodfordia fruticosa flowers collected in Myanmar led to the identification of anti-SmltD active flavonoids, kaempferol 3-O-(6''-galloyl)-ß-d-glucopyranoside (1), astragalin (2), and juglalin (3). Among them, 1 showed the most potent SmltD inhibitory activity. An enzyme steady-state kinetic study revealed that 1 exerted competitive inhibition with respect to ATP. The results of this study provided an attractive foundation for the further development of novel inhibitors of SmltD.
Assuntos
DNA Ligase Dependente de ATP/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Peptidoglicano/biossíntese , Woodfordia/química , DNA Ligase Dependente de ATP/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Estrutura Molecular , Peptidoglicano/química , Stenotrophomonas maltophilia/enzimologia , Relação Estrutura-AtividadeRESUMO
A new brominated pyrrolactam stylissaol A (1) together with four known analogues, 2-bromoaldisine, aldisine, spongiacidin D, and Z-hymenialdisine, were isolated from the EtOAc extract of marine sponge Stylissa massa collected in Myanmar. The absolute configuration at C-10 of 1 was determined as R by the electronic circular dichroism (ECD) data. Among the isolated compounds, 2-bromoaldisine showed anti-Viral Protein R (Vpr) activity against TREx-HeLa-Vpr cells with an effective dose of 10 µM and its potency was comparable to that of positive control damnacanthal.
Assuntos
Alcaloides/química , Antivirais/química , Poríferos/química , Alcaloides/isolamento & purificação , Alcaloides/metabolismo , Animais , Antivirais/isolamento & purificação , Antivirais/metabolismo , Dicroísmo Circular , Células HeLa , Humanos , Conformação Molecular , Mianmar , Poríferos/metabolismo , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismoRESUMO
Two new trihydroxy derivative of Δ8(14),15-isopimarane diterpenoids, shanpanootols G (1) and H (2), along with three known analogues were isolated from the ethyl acetate-soluble extract of Kaempferia pulchra rhizomes collected in Shan State of Myanmar. The structures of these compounds including their absolute configurations were elucidated by the combination of one dimensional (1D) and 2D-NMR spectroscopic methods, high resolution mass spectrometric technique, and the experimental and the calculated electronic circular dichroism (ECD) data. The isopimarane diterpenoids (1-5) were tested for their Viral protein R (Vpr) inhibitory activities against TREx-HeLa-Vpr cells. Shanpanootol H (2) and (1R,2S,5S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15-dien-7-one (4) exhibited anti-Vpr activities at the 5 µM treated dose.
Assuntos
Diterpenos/farmacologia , Rizoma/química , Zingiberaceae/química , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Diterpenos/química , Diterpenos/isolamento & purificação , Conformação Molecular , Mianmar , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismoRESUMO
A new menthane-type monoterpene, alpigalanol (1), together with four known terpenes (2-5) were isolated from the ethyl acetate soluble fraction of the 70 % ethanol extract of the Alpinia galanga rhizomes. The structure of 1 was determined by spectroscopic analyses, including 1D- and 2D-NMR. The extract of the A. galanga rhizomes and all isolated compounds (1-5) possessed Vpr inhibitory activities against the TREx-HeLa-Vpr cells at a concentration of 1.25â µM without showing any cytotoxicity.
Assuntos
Alpinia/química , Produtos do Gene vpr/antagonistas & inibidores , Monoterpenos/farmacologia , Rizoma/química , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Conformação Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Células Tumorais CultivadasRESUMO
The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.
Assuntos
Alcaloides/síntese química , Quinolinas/síntese química , Alcaloides/química , Animais , Anuros , Estrutura Molecular , Panamá , Quinolinas/química , EstereoisomerismoRESUMO
The rich history of prime numbers includes great names such as Euclid, who first analytically studied the prime numbers and proved that there is an infinite number of them, Euler, who introduced the function ζ(s)≡∑n=1∞n-s=∏pprime11-p-s, Gauss, who estimated the rate at which prime numbers increase, and Riemann, who extended ζ(s) to the complex plane z and conjectured that all nontrivial zeros are in the R(z)=1/2 axis. The nonadditive entropy Sq=k∑ipilnq(1/pi)(q∈R;S1=SBG≡-k∑ipilnpi, where BG stands for Boltzmann-Gibbs) on which nonextensive statistical mechanics is based, involves the function lnqz≡z1-q-11-q(ln1z=lnz). It is already known that this function paves the way for the emergence of a q-generalized algebra, using q-numbers defined as ⟨x⟩q≡elnqx, which recover the number x for q=1. The q-prime numbers are then defined as the q-natural numbers ⟨n⟩q≡elnqn(n=1,2,3,â¯), where n is a prime number p=2,3,5,7,⯠We show that, for any value of q, infinitely many q-prime numbers exist; for q≤1 they diverge for increasing prime number, whereas they converge for q>1; the standard prime numbers are recovered for q=1. For q≤1, we generalize the ζ(s) function as follows: ζq(s)≡⟨ζ(s)⟩q (s∈R). We show that this function appears to diverge at s=1+0, ∀q. Also, we alternatively define, for q≤1, ζq∑(s)≡∑n=1∞1⟨n⟩qs=1+1⟨2⟩qs+⯠and ζq∏(s)≡∏pprime11-⟨p⟩q-s=11-⟨2⟩q-s11-⟨3⟩q-s11-⟨5⟩q-sâ¯, which, for q<1, generically satisfy ζq∑(s)<ζq∏(s), in variance with the q=1 case, where of course ζ1∑(s)=ζ1∏(s).
RESUMO
A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D- and 2D-NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF-7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC50 values ranging from 23.6 to 75.5â µM against the three cell lines, and that 1H-indole-3-carboxylic acid showed cytotoxicity with an IC50 value of 89.2â µM against A549 cancer cell lines.
Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Ácidos Graxos/farmacologia , Poríferos/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas , VietnãRESUMO
2-Alkylquinolone (2AQ) alkaloids are pharmaceutically and biologically important natural products produced by both bacteria and plants, with a wide range of biological effects, including antibacterial, cytotoxic, anticholinesterase, and quorum-sensing signaling activities. These diverse activities and 2AQ occurrence in vastly different phyla have raised much interest in the biosynthesis pathways leading to their production. Previous studies in plants have suggested that type III polyketide synthases (PKSs) might be involved in 2AQ biosynthesis, but this hypothesis is untested. To this end, we cloned two novel type III PKSs, alkyldiketide-CoA synthase (ADS) and alkylquinolone synthase (AQS), from the 2AQ-producing medicinal plant, Evodia rutaecarpa (Rutaceae). Functional analyses revealed that collaboration of ADS and AQS produces 2AQ via condensations of N-methylanthraniloyl-CoA, a fatty acyl-CoA, with malonyl-CoA. We show that ADS efficiently catalyzes the decarboxylative condensation of malonyl-CoA with a fatty acyl-CoA to produce an alkyldiketide-CoA, whereas AQS specifically catalyzes the decarboxylative condensation of an alkyldiketide acid with N-methylanthraniloyl-CoA to generate the 2AQ scaffold via C-C/C-N bond formations. Remarkably, the ADS and AQS crystal structures at 1.80 and 2.20 Å resolutions, respectively, indicated that the unique active-site architecture with Trp-332 and Cys-191 and the novel CoA-binding tunnel with Tyr-215 principally control the substrate and product specificities of ADS and AQS, respectively. These results provide additional insights into the catalytic versatility of the type III PKSs and their functional and evolutionary implications for 2AQ biosynthesis in plants and bacteria.
Assuntos
Alcaloides , Evodia/enzimologia , Proteínas de Plantas , Plantas Medicinais/enzimologia , Policetídeo Sintases , Quinolonas , Alcaloides/biossíntese , Alcaloides/química , Cristalografia por Raios X , Evodia/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Medicinais/genética , Policetídeo Sintases/química , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Domínios Proteicos , Quinolonas/química , Quinolonas/metabolismoRESUMO
Daurichromenic acid (DCA) synthase catalyzes the oxidative cyclization of grifolic acid to produce DCA, an anti-HIV meroterpenoid isolated from Rhododendron dauricum We identified a novel cDNA encoding DCA synthase by transcriptome-based screening from young leaves of R. dauricum The gene coded for a 533-amino acid polypeptide with moderate homologies to flavin adenine dinucleotide oxidases from other plants. The primary structure contained an amino-terminal signal peptide and conserved amino acid residues to form bicovalent linkage to the flavin adenine dinucleotide isoalloxazine ring at histidine-112 and cysteine-175. In addition, the recombinant DCA synthase, purified from the culture supernatant of transgenic Pichia pastoris, exhibited structural and functional properties as a flavoprotein. The reaction mechanism of DCA synthase characterized herein partly shares a similarity with those of cannabinoid synthases from Cannabis sativa, whereas DCA synthase catalyzes a novel cyclization reaction of the farnesyl moiety of a meroterpenoid natural product of plant origin. Moreover, in this study, we present evidence that DCA is biosynthesized and accumulated specifically in the glandular scales, on the surface of R. dauricum plants, based on various analytical studies at the chemical, biochemical, and molecular levels. The extracellular localization of DCA also was confirmed by a confocal microscopic analysis of its autofluorescence. These data highlight the unique feature of DCA: the final step of biosynthesis is completed in apoplastic space, and it is highly accumulated outside the scale cells.
Assuntos
Fármacos Anti-HIV/metabolismo , Vias Biossintéticas , Cromanos/metabolismo , Ligases/metabolismo , Biocatálise , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Regulação da Expressão Gênica de Plantas , Proteínas de Fluorescência Verde/metabolismo , Cinética , Ligases/genética , Oxigênio/metabolismo , Filogenia , Compostos Fitoquímicos/metabolismo , Pichia/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo , Rhododendron/citologia , Rhododendron/genética , Rhododendron/metabolismo , Homologia Estrutural de Proteína , Nicotiana/citologiaRESUMO
The enantioselective total syntheses of lepadiformine marine alkaloids, azatricyclic natural products isolated from marine tunicates, were completed. These alkaloids have a unique chemical structure characterized by the trans-1-azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system). Here we found that a cycloisomerization reaction from functionalized linear substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in lepadiformines is promoted by a catalytic amount of mercury(II) triflate (Hg(OTf)2 ). The total syntheses of (-)-lepadiforminesâ A and B were achieved in 28 % and 21 % overall yields, respectively, through the novel cycloisomerization reaction. The syntheses of (+)- and (-)-lepadiformineâ C hydrochloride salts also enabled us to determine the absolute configuration of natural lepadiformineâ C. It has been found that a phenomenon of enantiodivergence occurs in lepadiformine alkaloids from a single species of marine tunicate, Clavelina moluccensis. The cytotoxic activities of synthesized lepadiformine hydrochloride salts and their synthetic intermediates were evaluated.
Assuntos
Alcaloides/síntese química , Antineoplásicos/síntese química , Urocordados/química , Alcaloides/farmacologia , Animais , Antineoplásicos/farmacologia , Organismos Aquáticos , Catálise , Proliferação de Células , Sobrevivência Celular , Células HT29 , Células HeLa , Humanos , Leucemia P388 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Estrutura Molecular , EstereoisomerismoRESUMO
Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca longepedunculata. However, their biological activities have not been fully investigated, since they are minor constituents in this plant. To evaluate the possibility of muchimangins as antibacterial agent candidates, five muchimangin analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the Brønsted acid-catalysis. The antibacterial assays against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs (±)-1,3,6,8-tetrahydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (1), (±)-1,3,6-trihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (2), and (±)-1,3-dihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (3) showed significant activities against S. aureus, with MIC values of 10.0, 10.0, and 25.0µM, respectively. Analogs (±)-1 and (±)-2 also exhibited antibacterial activities against B. subtilis, with MIC values of 50.0 and 12.5µM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity against S. aureus, with a MIC value of 10µM.
Assuntos
Antibacterianos/farmacologia , Compostos Benzidrílicos/farmacologia , Benzofenonas/química , Policetídeos/farmacologia , Xantonas/farmacologia , Antibacterianos/síntese química , Bacillus subtilis/efeitos dos fármacos , Compostos Benzidrílicos/síntese química , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Policetídeos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Xantonas/síntese químicaRESUMO
CONTEXT: Hedyotis pilulifera (Pit.) T.N. Ninh (Rubiaceae) has been used in Vietnamese ethnomedicine; the methanol extract exhibited antibacterial activity in our preliminary screening. OBJECTIVES: In this study, compounds from H. pilulifera were isolated and their antibacterial activity in vitro was evaluated. MATERIALS AND METHODS: The aerial parts of H. pilulifera (1.4 kg) were extracted with MeOH, suspended in water and ethyl acetate extract was chromatographed on a silica gel column. The structures of isolated compounds were elucidated by the combination analyses of spectroscopy including 1D-, 2D-NMR, HRMS and in comparison with the reported NMR data in the literature. All isolated compounds were evaluated for inhibitory effect using the microdilution method toward Staphylococcus aureus, Bacillus subtilis and Mycobacterium smegmatis, and MIC values were determined. RESULTS: Twenty compounds were isolated, including five triterpenoids, two steroids, two aromatic compounds, three fatty acids, one quinone derivative, one lignan glycoside, one ceramide and five glycolipids. Among these, oleanolic acid showed significant antibacterial activity against M. smegmatis with the MIC value of 2.5 µg/mL. Remarkably, rotungenic acid showed strong activity against S. aureus, B. subtilis, M. smegmatis with MIC values of 2.5, 2.5 and 1.25 µg/mL, respectively. Rotundic acid exhibited significant antibacterial activity against B. subtilis with the MIC value of 5 µg/mL. To the best of our knowledge, the antibacterial activity of rotungenic acid, stigmast-4-ene-3,6-dione and (2S,3S,4R,2'R)-2-(2'-hydroxytetracosanoylamino) octadecane-1,3,4-triol was reported for the first time. CONCLUSIONS: Oleanolic acid, rotungenic acid, and rotundic acid were considered to be useful for developing new antimicrobial therapeutic agents for human.
Assuntos
Antibacterianos/química , Antibacterianos/isolamento & purificação , Hedyotis/química , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Antibacterianos/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
Recently, the phenomenon of enantiodivergence was uncovered as a new phenomenon in the biosynthesis of natural products. In nature, chiral natural products are usually produced in optically active form, but both enantiomers sometimes arise in different genera and/or species or in a single species. Here we show through enantioselective total synthesis that the natural product isodehydrothyrsiferol shows partial enantiodivergency in that six of the nine or ten asymmetric centers are enantiomeric to those of other members of the marine squalene-derived triterpenoid thyrsiferol family. In addition, isodehydrothyrsiferol and dehydrothyrsiferol, which show partial enantiodivergency, were isolated from the same producer, the red alga Laurencia viridis. These results demonstrate that partial enantiodivergence can develop even between natural products originating from a single species.
Assuntos
Produtos Biológicos/síntese química , Furanos/síntese química , Laurencia/química , Piranos/síntese química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Furanos/química , Furanos/isolamento & purificação , Conformação Molecular , Piranos/química , Piranos/isolamento & purificação , EstereoisomerismoRESUMO
A new guaianolide sesquiterpene lactone, vernonilide A (1), and a new elemanolide sesquiterpene lactone, vernonilide B (2), were isolated from the seeds of Vernonia anthelmintica, together with three known elemanolide sesquiterpene lactones (3-5). The structures of the isolated compounds were elucidated on the basis of physicochemical evidences. Compounds 1, 3, and 4 showed strong antiproliferative activities against three human cancer cell lines (A549, HeLa, and MDA-MB-231), with IC50 values ranging from 0.10 to 1.00µM. In addition, 5 exhibited significant antiproliferative activities against HeLa and MDA-MB-231 cells, with IC50 values ranging from 1.90 to 2.20µM. The antiproliferative activities of the acetyl derivatives 6 and 7 prepared from 4 and 3, respectively, against the three cell lines were 4-10-fold weaker than the original activities.
Assuntos
Antineoplásicos/farmacologia , Lactonas/farmacologia , Sementes/química , Sesquiterpenos de Guaiano/farmacologia , Vernonia/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Povo Asiático , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1-15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity ((***)p <0.001) in comparing with that of the positive control, damnacanthal. The structure-activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.