RESUMO
Three new quinolizidine alkaloids (1 - 3), including one new naturally isoflavone and cytisine polymer (3), along with 6 known ones were isolated from the ethanol extract of Sophora tonkinensis Gagnep. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, HRESIMS, 1D and 2D NMR), combined with ECD calculations. The antifungal activity against Phytophythora capsica, Botrytis cinerea, Gibberella zeae, and Alternaria alternata of the compounds was evaluated in a mycelial inhibition assay. Biological tests indicated that compound 3 exhibited strong antifungal activity against P. capsica with EC50 values of 17.7 µg/ml.
Assuntos
Alcaloides , Sophora , Alcaloides Quinolizidínicos , Sophora/química , Antifúngicos/farmacologia , Raízes de Plantas/química , Alcaloides/química , Estrutura MolecularRESUMO
A new quinoline alkaloid, 5-hydroxy-6-methoxy-N-methyl-2-phenylquinoline-4-one (1), and seventeen known quinoline alkaloids (2-18) were isolated from the roots of Orixa japonica. The structure of 1 was determined by analysis of spectroscopic data. Among them, compounds 2, 3, and 13 were isolated from this plant for the first time. All isolates were screened for the anti-pathogenic fungi activities, including Rhizoctonia solani, Magnaporthe oryzae, and Phomopsis sp. The results showed that five compounds (4, 8, 10, 11, and 12) exhibited significant anti-pathogenic fungi effects at 50.0 µg/mL. In special, compound 10 exhibited the best antifungal activities toward R. solani and M. oryzae with the IC50 values of 37.86 and 44.72â µM, respectively, better than that of the positive control, hymexazol (IC50 121.21 and 1518.18â µM, respectively). Moreover, eleven new quinoline alkaloids derivatives (12a-12k) were designed and synthesized to investigate the structure-activity relationships (SARs). The SARs analysis indicated that the furo[2,3-b]quinoline skeleton and the methoxy at C-7 (compounds 8, 11, and 12) played a key role for improving the antifungal activities.
Assuntos
Alcaloides , Quinolinas , Antifúngicos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Quinolinas/química , FungosRESUMO
To discover novel and effective antifungal candidates, a series of new curcumol derivatives were designed, synthesized, and evaluated their antifungal activity against five phytopathogenic fungi by the mycelium growth rate method. Derivatives c4, c22 and c23 exhibited excellent antifungal activity against Phomopsis sp. with EC50 values of 3.06, 3.07, and 3.16â µM, respectively. Specifically, compound c4 exhibited the strongest antifungal activity against Phomopsis sp., which was 44 times that of pyrimethanil (EC50 =134.37â µM). The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that compound c4 could cause cell senescence and death of Phomopsis sp. by changing the normal hyphal morphology and disrupting the normal metabolism of hyphal cells. Moreover, compound c4 showed excellent curative effect against Phomopsis sp. on kiwifruit. These findings confirmed that compound c4 has great potential as a potent antifungal agent.
Assuntos
Antifúngicos , Sesquiterpenos , Antifúngicos/farmacologia , Relação Estrutura-Atividade , Fungos , Sesquiterpenos/farmacologiaRESUMO
Two new ursane-type triterpenes, eburnealactones A and B (1 and 2), one new flavonoid, eburneatin A (6), and one new phenylethanoid glycoside, chiritoside D (7), along with 9 known compounds (3-5, 8-13) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC50 values of 9.57â µM and 8.30â µM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC50 values of 30.70â µM and 38.22â µM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC50 values of 19.69â µM, 16.44â µM, 18.07â µM, 11.51â µM and 18.15â µM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC50 values of 24.06â µM.
Assuntos
Antineoplásicos , Triterpenos , Humanos , Estrutura Molecular , Glicosídeos/química , Antineoplásicos/farmacologia , Flavonoides , Células A549 , Triterpenos/farmacologia , Triterpenos/químicaRESUMO
Two new isoflavones (1 and 2), as well as eight known ones were isolated from the roots of Sophora tonkinensis Gagnep. Compound 1 represents an unprecedented polymerization pattern constructed by isoflavone and cytisine. Their structures were elucidated by comprehensive spectroscopic data analysis, combined with ECD calculations. Compound 1 displayed significant anti-tobacco mosaic virus (TMV) activity compared with the positive control ningnanmycin. Moreover, compound 6 exhibited potent α-glucosidase inhibitory activity with IC50 value of 47.4 mg/L.
Assuntos
Alcaloides , Isoflavonas , Sophora , Isoflavonas/farmacologia , Sophora/química , Raízes de Plantas/química , Alcaloides/química , Quinolizinas/análiseRESUMO
Six novel Maillard reaction products (MRPs) (1-6) were isolated from the processed Thermopsis lanceolata R. Br. seed extract, along with one biogenetically related intermediate (7). Compounds 1-4 possessed three rare dimerization patterns constructed by cytisine, whereas compounds 5 and 6 represented the first example of the addition products of cytisine and 5,6-dihydroxy-4-hexanolide. Their structures were elucidated by comprehensive spectroscopic data analysis and quantum chemistry calculations including GIAO 13C{1H} NMR and ECD calculation, combined with single-crystal X-ray diffraction analysis. Biologically, compound 3 displayed significant anti-tobacco mosaic virus activity compared with the positive control ningnanmycin.
Assuntos
Vírus do Mosaico do Tabaco , Antivirais/química , Produtos Finais de Glicação Avançada , Extratos Vegetais/químicaRESUMO
Hyperpatone A (1), a highly oxidated polycyclic polyprenylated acylphloroglucinol (PPAP), along with a biosynthesized related PPAP (2) was isolated from Hypericum patulum under the guidance of LC-MS investigation. Architecturally, compound 1 represents the first PPAP with an unprecedented 8/6/5/6/5 pentacyclic skeleton and an intramolecular peroxy bridge, which might be derived from the [3.3.1]-type bicyclic polyprenylated acylphloroglucinol via the critical Baeyer-Villiger oxidation, decarboxylation, and intramolecular cyclization. The structures were established by extensive spectroscopic analysis, ACD software calculation, and quantum chemical computations. A plausible biogenetic pathway of 1 and 2 was also proposed. Importantly, both compounds exhibited moderate cytotoxic activities against the HEL cell line with the IC50 values ranging from 10.2 to 19.2 µM. Moreover, compound 1 showed an inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells at a lower concentration of 5 or 1 µM.
Assuntos
Hypericum , Estrutura Molecular , Hypericum/química , Floroglucinol/química , EsqueletoRESUMO
Three new compounds named cynansteroid A (1), cynansteroid B (2) and cynansteroid C (3), together with nine known C21 -steroidal pregnane sapogenins (4-12) were isolated from the hydrolytic extract of the roots of Cynanchum auriculatum. The structures of cynansteroid A-C (1-3) were ascertained via the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and the calculated and experimental ECD data of cynansteroid B (2). Compound 11 displayed moderate inhibitory activity toward Verticillium dahliae Kleb (IC50 =37.15â µM), furthermore, compounds 11 and 12 showed significant inhibitory activity against Phomopsis sp. (IC50 =16.49â µM and 17.62â µM, respectively).
Assuntos
Cynanchum , Sapogeninas , Cynanchum/química , Glicosídeos/química , Raízes de Plantas/química , Pregnanos/química , Pregnanos/farmacologiaRESUMO
Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03-8.40â µM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.
Assuntos
Aglaia , Antineoplásicos Fitogênicos , Antineoplásicos , Triterpenos , Aglaia/química , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Dicroísmo Circular , Humanos , Estrutura Molecular , Extratos Vegetais/química , Triterpenos/químicaRESUMO
Two new (1 and 2) cytisine-type alkaloids that were chemically inseparable isomers (present in a 1:1 ratio) were identified from the seeds of Thermopsis lanceolata R. Br. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS) and ECD calculation. Compound 1 displayed significant anti-tobacco mosaic virus (TMV) activity, while compounds 1 and 2 displayed moderate insecticidal activities against Aphis fabae with LC50 value of 43.15 and 46.47 mg/L, respectively.
Assuntos
Alcaloides , Fabaceae , Estrutura Molecular , Quinolizinas/farmacologia , Alcaloides/farmacologia , Alcaloides/química , Azocinas , Sementes , Antivirais/químicaRESUMO
Hypermonins A-D (1-4), four rearranged nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) with unprecedented skeletons, together with two new biosynthesis related PPAPs (5 and 6) were isolated and identified from the flowers of Hypericum monogynum. Hypermoins A-D represented the first examples of highly modified norPPAPs characterized by a rare 7/6/6/5-tetracyclic system. From the biogenic synthesis pathway analysis, all isolates shared the same biosynthetic intermediate, and the addition of two methyls or one methyl to this intermediate through methyltranferase could generate different types of PPAPs (1-7). Their planner structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. All isolates potentially reversed multidrug resistance (MDR) activity in both two cancer cells, HepG2/ADR and MCF-7/ADR. Specifically, hypermoin E (5) and hyperielliptone HA (7) were found to be the best MDR modulators with the reversal fold ranging from 41 to 236, which is higher than the positive control verapamil.
Assuntos
Hypericum , Cristalografia por Raios X , Flores , Estrutura Molecular , Floroglucinol/farmacologiaRESUMO
Hypsampsone A (1) and hyperhexanone F (2), two novel seco-polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum sampsonii. Hypsampsone A (1) features the first spirocyclic system fused with 5/6/5/5 tetracyclic skeleton. Hyperhexanone F (2) represents the second novel 1,2-seco-bicyclo[3.3.1]-PPAP skeleton. Their structures were established by extensive spectroscopic analysis, computer-assisted structure elucidation software, and calculated electronic circular dichroism spectra. A plausible biogenetic pathway of 1 was also proposed. Compounds 1 and 2 showed moderate multidrug resistance reversal activity to adriamycin (ADR) resistant cancer cell lines, HepG2/ADR and MCF-7/ADR, with the fold-reversals ranging from 16 to 38 at noncytotoxic concentration of 10 µM.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Hypericum/química , Floroglucinol/química , Floroglucinol/farmacologia , Prenilação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Modelos Moleculares , Conformação MolecularRESUMO
A new polycyclic polyprenylated acylphloroglucinol (PPAP), hypermonin C (1), along with nine known PPAPs (2-10) were obtained from the leaves and twigs of Hypericum monogynum. The structures of the isolates were determined on the basis of extensive spectroscopic analysis. The neuroprotective effects of the isolates against several chemical-induced injuries in SH-SY5Y and PC12 cells were assessed, and most of the compounds exhibited significant protective effects at 10 µg/ml. Especially, three compounds (1, 3, and 7) showed excellent neuroprotective activity with a cell viability of 92.4% â¼ 95.8% in KCl-induced SH-SY5Y cell injury. Their preliminary structure-activity relationship was also discussed and the configuration of substituent in furohyperforin may be critical for the neuroprotective activity of PPAP derivatives.
Assuntos
Hypericum , Fármacos Neuroprotetores , Animais , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Células PC12 , Floroglucinol/farmacologia , Folhas de Planta , RatosRESUMO
Two new compounds, including one new arylbenzofuran (1) and one new pterocarpanoid (2), along with nine known ones, were isolated from the seeds of Sophora tonkinensis. The structures of the new compounds were elucidated based on a comprehensive spectroscopic data analysis. Compounds 2 and 3 exhibited good anti-tobacco mosaic virus (TMV) activities with the protective inhibition rate of 69.62% and 68.72% respectively, at concentration of 100 µg/ml.
Assuntos
Sophora , Vírus do Mosaico do Tabaco , Antivirais/farmacologia , Estrutura Molecular , SementesRESUMO
A series of novel parthenolide-thiazolidinedione hybrids have been synthesized via a click chemistry-mediated coupling between parthenolide and thiazolidinedione, and evaluated for their cytotoxic activities. The results indicated that all the hybrids showed moderate cytotoxic effects on human cancer cell lines, including human erythroleukemia cell line (HEL), prostate (PC3), and breast (MDA-MB-231) by MTT assay. In particular, compound VI-6 exhibited the best cytotoxic activities against the MDA-MB-231 cells with IC50 value of 2.07 µM, which was about eight times more active than that of the original compound (PTL). These interesting results might be used to develop novel lead scaffolds for potential anticancer agents.
Assuntos
Antineoplásicos , Tiazolidinedionas , Linhagem Celular Tumoral , Proliferação de Células , Química Click , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , SesquiterpenosRESUMO
BACKGROUND: MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. METHOD: A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541-43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia. RESULTS: Compounds A1541-43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541-43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541-43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541-43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541-43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia. CONCLUSIONS: This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Eritroblástica Aguda/tratamento farmacológico , Limoninas/farmacologia , Limoninas/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melia azedarach/química , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células K562 , Leucemia Eritroblástica Aguda/mortalidade , Leucemia Eritroblástica Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Folhas de Planta/química , Transdução de Sinais/efeitos dos fármacos , Taxa de SobrevidaRESUMO
Two new 6-norpolycyclic polyprenylated acylphloroglucinols (PPAPs), hypermonins A (1) and B (2), featuring an undescribed decahydroindeno[1,7-bc]furan ring system, were isolated from the leaves and twigs of Hypericum monogynum. These compounds are a pair of epimers with opposite configurations at the C-5 position. Their structures, including their absolute configurations, were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway of 1 and 2 was also proposed. Compound 1 exhibited a significant protective effect against corticosterone-induced injury in PC12 cells.
Assuntos
Hemiterpenos/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Hypericum/química , Fármacos Neuroprotetores/farmacologia , Floroglucinol/análogos & derivados , Floroglucinol/farmacologia , Animais , Linhagem Celular Tumoral , Hemiterpenos/química , Hemiterpenos/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Modelos Químicos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Floroglucinol/química , Floroglucinol/isolamento & purificação , Folhas de Planta/química , Ratos , EstereoisomerismoRESUMO
During the screening of natural anti-inflammatory agent, we identified some C21-steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4-initiatedinflammatory responses respectively. Treatment with active compounds 10, 2j and 3p failed to impact tumor necrosis factor-α (TNF-α) induced nucleus translocation of NF-κB p65 subunit. However, these compounds regulated distinct canonical or non-canonical NF-κB family members. Ectopic expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory activity of the compounds on production of pro-inflammatory cytokines downstream of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLR-initiated innate immunity through TRAF6 with differential regulation of NF-κB family proteins.
Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/antagonistas & inibidores , Sapogeninas/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Sapogeninas/síntese química , Sapogeninas/química , Relação Estrutura-AtividadeRESUMO
The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034 µM, respectively.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Esteroides/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Ascomicetos/crescimento & desenvolvimento , Cynanchum/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Conformação Molecular , Esteroides/síntese química , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7.