RESUMEN
Two new triterpenoid saponins, namely camsinsaponins A and B (1, 2), along with two known congeners (3, 4) were isolated from Camellia sinensis flowers. Their structures were determined by extensive spectroscopic data. All compounds were assessed for antifungal bioactivity against Candida albicans, Candida glabrata, and Candida tropicalis. Compounds 1-4 showed excellent inhibitory effects. Notably, in regard to compounds 1 and 2, their MIC values against C. albicans were close to those of the positive control, fluconazole. Furthermore, the inhibitory elements of compounds 1-4 on C. glabrata were better than those of fluconazole. The aforementioned findings offer valuable insights for future development of novel therapeutic strategies against drug-resistant infections.
Asunto(s)
Antifúngicos , Camellia sinensis , Flores , Pruebas de Sensibilidad Microbiana , Saponinas , Triterpenos , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Flores/química , Camellia sinensis/química , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Estructura Molecular , Candida albicans/efectos de los fármacosRESUMEN
Chlamydia are obligate intracellular bacterial pathogens affecting humans and animals, causing miscarriage, stillbirth, or weak fetuses in the late stages of pregnancy of goats and sheep. Because there is no commercial vaccine for chlamydia in animals, drug treatment has become the most effective curative method. Natural products, also known as secondary metabolites, are becoming one of the main sources used in new drug development because of their structural diversity and biodiversity. In natural products, plant sources play a major role in the development process of new drugs. In this study, five undescribed highly oxygenated bisabolane sesquiterpenes (Pararubin W, Pararubin X, Pararubin Y., Pararubin Z, and Pararubin AA) were isolated from whole plants of Ligularia narynensis. Their chemical structures were determined via analyses of HRESIMS, IR, 1D, and 2D NMR data, along with the assignment of their relative configurations. These compounds were tested for their anti-chlamydial activity. The results show that compounds 1 and 5 inhibited the growth of Chlamydia abortus in host cells in a dose-dependent manner.
Asunto(s)
Antibacterianos , Asteraceae , Sesquiterpenos , Asteraceae/química , Antibacterianos/farmacología , Antibacterianos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Animales , Humanos , Chlamydia/efectos de los fármacos , Chlamydia/crecimiento & desarrollo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Estructura Molecular , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
In the present study, we first discovered that the 70% ethanol extract of Ypsilandra thibetica significantly inhibited Arabidopsis root growth. Through a bioactivity-guided strategy, 18 rare 23-spirocholestane derivatives (1-18), including 12 new ones (1-12), featuring a dioxane ring between C-24/C-23 of the aglycone moiety and C-1'/C-2' of the d-fucose ligand, were obtained from the strongest active elution fraction. Their structures were elucidated via a comprehensive method of MS and NMR spectroscopy, single-crystal X-ray diffraction, and chemical methods. Evaluation of their inhibitory effects of all isolates on Arabidopsis root growth revealed that 5/6, 3/4, 1, and 2 exhibited pronounced activity, with EC50 values of 6.89, 9.13, 18.01, and 26.83 µM, respectively. Then, a preliminary structure-activity relationship (SAR) analysis of these compounds was conducted. Furthermore, transcriptome data indicated that Arabidopsis responded to the stress caused by these bioactive compounds through the modulation of ethylene and auxin signaling pathways and the activation of various detoxification-related genes. Finally, the herbicidal evaluation showed that 3/4 and 5/6 significantly inhibited the root growth of Echinochloa crusgalli, while 3/4 remarkably suppressed the root growth of Lolium multiflorum. These findings highlight that 23-spirocholestane derivatives represent promising candidates for the development of new bioherbicides.
Asunto(s)
Arabidopsis , Extractos Vegetales , Raíces de Plantas , Arabidopsis/crecimiento & desarrollo , Arabidopsis/efectos de los fármacos , Raíces de Plantas/química , Raíces de Plantas/crecimiento & desarrollo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Estructura Molecular , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/química , Ácidos Indolacéticos/química , Ácidos Indolacéticos/farmacologíaRESUMEN
Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 µmol·L~(-1).
Asunto(s)
Ligusticum , Óxido Nítrico , Ligusticum/química , Animales , Ratones , Células RAW 264.7 , Benzofuranos/química , Benzofuranos/farmacología , Benzofuranos/aislamiento & purificación , Estructura Molecular , Macrófagos/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
This study investigated the secondary metabolites in the product of rice fermentation with Alternaria alternata and their activity of down-regulating thymosin beta 10(TMSB10) protein expression. The secondary metabolites of A. alternata were separated and purified by various chromatographic separation techniques, including silica gel column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Their structures were identified by spectral techniques such as nuclear magnetic resonance spectroscopy(NMR), infrared spectroscopy(IR), and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and comparison with literature data. A total of 10 compounds were isolated and identified, including two new compounds(1S,3S)-2,3-dihydro-3,6-dihydroxy-8-methoxy-1-methylcyclopenta[c][2]benzopyran-5(1H)-one(1), 3,3a, 6-trihydroxy-8-methoxy-1-methyl-2,3,3a, 9b-tetrahydrocyclopenta[c]isochromen-5(1H)-one(2), and the eight known compounds are alternariol 9-methyl ether(3), 1-deoxyrubralactone(4),(3aR)-3,3a-dihydro-1,6-dihydroxy-8-methoxy-3a-methylcyclopenta[c][2]benzopyran-2,5-dione(5), altechromone A(6), alternariol(7), altenuene(8), altenusin(9), and 3'-hydroxyalternariol 5-O-methyl ether(10). The effects of these compounds on TMSB10 expression were tested. Compound 7 showed a significant down-regulation effect on TMSB10 expression with an inhibition rate of 40.5%. The results showed that benzopyrone compounds of A. alternata have the activity of down-regulating the expression of TMSB10 protein, providing theoretical basis and research value for the study of non-small cell lung cancer.
Asunto(s)
Alternaria , Regulación hacia Abajo , Alternaria/química , Regulación hacia Abajo/efectos de los fármacos , Estructura Molecular , Metabolismo Secundario , Espectroscopía de Resonancia MagnéticaRESUMEN
The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)µmol·L~(-1) and(881.82±42.31)µmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Asunto(s)
Glicósidos , Juglandaceae , Hojas de la Planta , Tetralonas , Hojas de la Planta/química , Glicósidos/química , Juglandaceae/química , Tetralonas/química , Medicamentos Herbarios Chinos/química , Estructura Molecular , Antioxidantes/química , Cromatografía Líquida de Alta PresiónRESUMEN
Fluorescence imaging and phototherapy in the near-infrared window (NIR, 650-1700 nm) have attracted great attention for biomedical applications due to their minimal invasiveness, ultra-low photon scattering and high spatial-temporal precision. Among NIR emitting/absorbing organic dyes, xanthene derivatives with controllable molecular structures and optical properties, excellent fluorescence quantum yields, high molar absorption coefficients and remarkable chemical stability have been extensively studied and explored in the field of biological theranostics. The present study was aimed at providing a comprehensive summary of the progress in the development and design strategies of xanthene derivative fluorophores for advanced biological phototheranostics. This study elucidated several representative controllable strategies, including electronic programming strategies, extension of conjugated backbones, and strategic establishment of activatable fluorophores, which enhance the NIR fluorescence of xanthene backbones. Subsequently, the development of xanthene nanoplatforms based on NIR fluorescence for biological applications was detailed. Overall, this work outlines future efforts and directions for improving NIR xanthene derivatives to meet evolving clinical needs. It is anticipated that this contribution could provide a viable reference for the strategic design of organic NIR fluorophores, thereby enhancing their potential clinical practice in future.
Asunto(s)
Colorantes Fluorescentes , Rayos Infrarrojos , Xantenos , Xantenos/química , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Nanomedicina Teranóstica , Imagen Óptica , Animales , Fototerapia/métodos , Estructura Molecular , Diseño de FármacosRESUMEN
Marchantia polymorpha L., also known as common liverwort or umbrella liverwort, is a spore-forming plant belonging to the Marchantiaceae family. This thallose liverwort has gained importance as a model plant, mainly because of its global distribution and easy and rapid in vitro culturing. A review of the literature shows that the major compounds in this species are undoubtedly sesquiterpenoids and bisbibenzyls. Among the sesquiterpenoids, it is worth mentioning cuparenes, chamigranes, and thujopsanes. Compounds belonging to these classes were found in specimens from Japan, China, Poland, Germany, and India and could be the chemical markers of this liverwort species. The key secondary metabolite of M. polymorpha is a macrocyclic bisbibenzyl, marchantin A. Marchantin-type aromatic compounds, together with other bisbibenzyls, such as riccardin D, isoriccardin C, or perrottetin E, demonstrated antifungal and antibacterial properties in various studies. In this review, we summarize the current knowledge on the diversity of compounds produced by M. polymorpha, emphasizing chemical variability depending on the origin of the plant material. Moreover, the biological activity of extracts obtained from this liverwort species, as well as single secondary metabolites, are described.
Asunto(s)
Marchantia , Marchantia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Bibencilos/química , Bibencilos/farmacología , Antifúngicos/farmacología , Antifúngicos/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Estructura MolecularRESUMEN
Eriobotrya japonica (Thunb.) Lindl., commonly known as loquat, is a plant belonging to the Rosaceae family. While its fruit is widely consumed as food and used in traditional medicine, research on other parts of the plant remains insufficient. Therefore, the chemical constituents and biological activities of its leaves were investigated. Phytochemical analysis of E. japonica leaves identified 30 compounds, including flavonoids, phenolics, and megastigmanes. The flavonoids isolated from the leaves include flavones, flavans, flavolignans, flavonoid glycosides, and coumaroyl flavonoid glycosides. Coumaroyl flavonoid rhamnosides were characteristically present in E. japonica leaves, and the configurations of coumaric acids, as well as the binding position to the rhamnose in each compound, were identified through detailed NMR analysis. Notably, three of them were isolated from this plant for the first time. Phenolic compounds were found to be present as conjugates with organic acids, such as quinic acid, shikimic acid, and glucose. Flavonoid and phenolic compounds demonstrated significant antioxidant and α-glucosidase inhibitory effects, whereas megastigmanes showed little activity. Notably, coumaroyl flavonoid rhamnosides, which consist of flavonoids combined with the phenolic acid, coumaric acid, exhibited excellent anti-diabetic effects. Further molecular docking analysis confirmed that these compounds effectively bind to the α-glucosidase enzyme. In conclusion, the present study identified flavonoid and phenolic components with various structures in E. japonica leaves and clarified their anti-diabetic and antioxidant effects. These findings support the beneficial potential of E. japonica leaves for the treatment and/or prevention of metabolic diseases.
Asunto(s)
Antioxidantes , Eriobotrya , Flavonoides , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Fenoles , Hojas de la Planta , Eriobotrya/química , Hojas de la Planta/química , Flavonoides/química , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Fenoles/química , Fenoles/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Estructura Molecular , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/químicaRESUMEN
Favelines, benzocycloheptene diterpenes exclusively found in Cnidoscolus quercifolius, have shown promising anticancer properties, particularly phyllacanthone. Nevertheless, the isolation of these compounds remains challenging due to their similar polarity. The use of centrifugal partition chromatography (CPC) has enabled the quick and efficient purification of phyllacanthone from C. quercifolius crude extract with a yield of 4.5% (w/w) and a purity of 83%. Favelines-enriched fractions were also obtained and purified by preparative HPLC, resulting in the isolation of faveline, isofavelol, and deoxofaveline. In addition, phyllacanthone B, a previously unreported derivative, was identified and characterized. Pharmacological evaluations revealed the significant anti-melanoma activity of purified metabolites, with distinct structure-activity relationships. These results shed light on the mechanism of action of favelines, suggesting their potential as hits for the development of novel anticancer agents.
Asunto(s)
Diterpenos , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Cromatografía Líquida de Alta Presión , Animales , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Línea Celular Tumoral , Cupressaceae/química , Relación Estructura-Actividad , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Centrifugación , Proliferación Celular/efectos de los fármacos , Ratones , Estructura MolecularRESUMEN
Bilirubin (BR) is a water-insoluble product of heme catabolism in mammals. Elevated blood concentrations of BR, especially in the neonatal period, are treated with blue-green light phototherapy. The major mechanism of BR elimination during phototherapy is photoisomerization, while a minor, less studied mechanism of degradation is oxidation. In this work, we studied the oxidation of the bilirubin model tetramethyl-dipyrrinone (Z-13) by singlet oxygen in methanol using UV-vis and ESI-MS spectroscopy, resulting in propentdyopents as the main oxidation products. We also identified two additional intermediates that were formed during the reaction (hydroperoxide 21a and imine 17). The structure of the hydroperoxide was confirmed by helium-tagging IR spectroscopy. Such reaction intermediates formed during the oxidation of BR or bilirubin models have not been described so far. We believe that this work can be used as a first step in studying the complex oxidation mechanism of BR during phototherapy.
Asunto(s)
Oxidación-Reducción , Oxígeno Singlete , Oxígeno Singlete/química , Procesos Fotoquímicos , Estructura Molecular , Bilirrubina/química , Dipirona/químicaRESUMEN
The apicomplexan parasite Toxoplasma gondii causes toxoplasmosis, a ubiquitous and cosmopolitan parasitosis, generally asymptomatic and potentially dangerous for the fetus and highly immunocompromised patients. Pyrimethamine and sulfadiazine, supplemented with folic acid, are the drugs of choice to treating the disease, but they produce severe side effects and treatments fail due to drug resistance. New anti-Toxoplasma compounds are needed, and natural compounds can be a good source for obtaining them. The antiparasitic activity of 40 polar and non-polar extracts of eight antiparasitic medicinal plants used in Côte d'Ivoire, and selected based on ethnopharmacological survey, were evaluated in vitro against T. gondii. Among them, the hydromethanolic extract of the Elaeis guineensis leaves exhibited the best parasite growth inhibition (94% ± 0.07) at 25 µg/mL without being cytotoxic at the same dose. The fractionation of this extract did not allow the recovery of antitoxoplasmic activity in its individualized fractions. The 13C-NMR based dereplication of this extract and the purification of two fractions highlighted the presence of saccharides (1-2), aliphatic acids (3 and 8-11), cardanols (12-13), triterpene (14), sterol (15), nor-sesquiterpene (16), megastigman derivatives (7 and 17-19), glycosylated benzyl (20-21), flavonoids (4-6 and 22), pseudoalkaloid (23), and allyl glycoside (24). Nine compounds 1-9 were identified during the dereplication process, whereas fifteen compounds 10-24 were identified after purification and four of them were undescribed (16-18 and 20). A synergistic effect between these metabolites is thought to be responsible for the anti-Toxoplasma activity. However, further studies should be carried out to confirm and explain this synergistic or antagonistic effect between the identified compounds.
Asunto(s)
Glicósidos , Hojas de la Planta , Toxoplasma , Hojas de la Planta/química , Toxoplasma/efectos de los fármacos , Côte d'Ivoire , Glicósidos/química , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Antiprotozoarios/farmacología , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Estructura Molecular , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
New Zealand's unique indigenous flora has evolved due to its geographical isolation in the Southern Hemisphere. In the 250 years, since European colonisation commenced, much indigenous flora has been replaced by plants largely of Northern Hemisphere origin including poplar species and pine. There are however still a few large areas of principally native flora. The honeybee (Apis mellifera) was introduced to New Zealand in 1839, so has no evolutionary link to the New Zealand indigenous flora. New Zealand propolis from areas in which honeybees have access to poplar and other Northern Hemisphere species is similar in chemical profile to Northern Hemisphere propolis. However, when honeybees were placed in an extensive area of native flora, Te Urewera in the North Island,the chemical profile of propolis produced was vastly different. This "endemic" propolis was characterised by the presence of diterpenoids in contrast to the flavonoids found in poplar-type propolis. These diterpenoids, isocupressic acid, acetyl isocupressic acid, manool, torulosal, communic acid and ferruginol, were characterised by GC-MS and by NMR spectroscopy of the isolated compounds. The "endemic" propolis has commonality with propolis of the Mediterranean-type as well as some Brazilian propolis. Investigation of the bioactivity of a sample of the "endemic" propolis revealed good antioxidant behaviour with a TEAC of 1481 mgtrolox g-1, dose-dependent inhibition of mitochondrial dehydrogenase activity, inhibition of superoxide production with an IC50 of 262 µg mL-1 and inhibition of methicillin resistant and methicillin sensitive S. aureus. Much of this bioactivity can be attributed to the presence of the diterpenoids.
Asunto(s)
Bosques , Própolis , Própolis/química , Própolis/farmacología , Nueva Zelanda , Abejas , Animales , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/química , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/químicaRESUMEN
Daphne retusa belongs to the Daphne genus of Thymelaeaceae, which is widespread in northwest China, and its roots and stem bark are commonly used in Chinese folk medicine to treat rheumatism and congestion. In this study, four new (1-4) and eleven known (5-15) flavones were isolated from the branches and leaves of Daphne retusa, including six monomeric flavones (2-7) and nine dimeric flavones (1, 8-15). On the basis of chemical evidence and spectral data analysis (UV, ECD, NMR, and HR-ESI-MS), the structures of compounds 1-4 was elucidated. Furthermore, all compounds have been tested for their inhibitory effects on NO production in LPS-induced RAW 264.7 cells, and compounds 2 and 8 showed obvious inhibitory effect.
Asunto(s)
Antiinflamatorios , Daphne , Flavonas , Óxido Nítrico , Hojas de la Planta , Tallos de la Planta , Ratones , Flavonas/farmacología , Flavonas/aislamiento & purificación , Flavonas/química , Células RAW 264.7 , Daphne/química , Hojas de la Planta/química , Animales , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Óxido Nítrico/metabolismo , China , Tallos de la Planta/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificaciónRESUMEN
Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance to conventional therapies, leading to poor patient outcomes. This challenges the efficiency of photodynamic therapy (PDT), which relies on the generation of cytotoxic reactive oxygen species (ROS) through the irradiation of a photosensitizer (PS), a process partially dependent on oxygen levels. In this work, we introduce a novel family of potent PSs based on ruthenium(II) polypyridyl complexes with 2,2'-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY complexes exhibit outstanding in vitro cytotoxicity against CT-26 cancer cells when irradiated with light within the phototherapeutic window, achieving nanomolar potency in both normoxic and hypoxic conditions while remaining nontoxic in the dark, leading to impressive phototoxic indices (>30,000). Their ability to generate both Type I and Type II ROS underpins their exceptional PDT efficiency. The lead compound of this study, SCV49, shows a favorable in vivo pharmacokinetic profile, excellent toxicological tolerability, and potent tumor growth inhibition in mice bearing subcutaneous CT-26 tumors at doses as low as 3 mg/kg upon irradiation with deep-red light (660 nm). These results allow us to propose SCV49 as a strong candidate for further preclinical development, particularly for treating large hypoxic solid tumors.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rutenio , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Rutenio/química , Rutenio/farmacología , Ligandos , Animales , Ratones , Humanos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Piridinas/química , Piridinas/farmacología , Hipoxia Tumoral/efectos de los fármacos , Estructura Molecular , Proliferación Celular/efectos de los fármacosRESUMEN
Lespedeza bicolour Turcz. is a traditional medicinal plant with a wide range of ethnomedicinal values. The main components of L. bicolour essential oil (EO) were ß-pinene (15.41%), ß-phellandrene (12.43%), and caryophyllene (7.79%). The EO of L. bicolour showed antioxidant activity against ABTS radical and DPPH radical with an IC50 value of 0.69 ± 0.03 mg/mL and 10.44 ± 2.09 mg/mL, respectively. The FRAP antioxidant value was 81.96 ± 6.17 µmol/g. The EO had activities against acetylcholinesterase, α-glucosidase, and ß-lactamase with IC50 values of 309.30 ± 11.16 µg/mL, 360.47 ± 35.67 µg/mL, and 27.54 ± 1.21 µg/mL, respectively. Molecular docking showed methyl dehydroabietate docked well with all tested enzymes. Sclareol and (+)-borneol acetate showed the strongest binding affinity to α-glucosidase and ß-lactamase, respectively. The present study provides a direction for searching enzyme inhibitors for three tested enzymes and shows L. bicolour EO possesses the potential to treat a series of diseases.
Asunto(s)
Acetilcolinesterasa , Antioxidantes , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos , Aceites Volátiles , alfa-Glucosidasas , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , alfa-Glucosidasas/metabolismo , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , beta-Lactamasas/metabolismo , Estructura Molecular , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Picratos/antagonistas & inhibidores , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Simulación del Acoplamiento Molecular , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Ácidos Sulfónicos , BenzotiazolesRESUMEN
Japanese dodder (Cuscuta japonica Choisy) is a parasitic plant with diverse pharmaceutical properties that has demonstrated great promise for the development of dietary supplements and herbal medicines. A systematic phytochemical investigation of dodder seeds yielded 12 previously undescribed aromatic glycosides (1-12) and eight known constituents (13-20) from various groups, including phenolics, flavonoids, and lignan glycosides. Compound structures were determined using a combination of high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Moreover, quantum mechanics-driven 1H iterative full spin analysis revealed intricate NMR spectral details for the isolated glycosides, including multiplicities and coupling constants that were previously ambiguous, providing crucial insight into the presence of higher-order resonance effects in the sugar units as well as long-range couplings in unsaturated molecules. Furthermore, the abilities of the plant extract as well as compounds 1, 2, 4-7, 10, 11, and 14-20 to restore cell viability and reduce reactive oxygen species production in SH-SY5Y cells suggest that C. japonica and its isolates are potential antioxidant neuroprotective therapeutic candidates.
Asunto(s)
Supervivencia Celular , Cuscuta , Glicósidos , Peróxido de Hidrógeno , Estrés Oxidativo , Fenoles , Semillas , Semillas/química , Humanos , Glicósidos/farmacología , Glicósidos/química , Glicósidos/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Fenoles/farmacología , Fenoles/química , Fenoles/aislamiento & purificación , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Estructura Molecular , Supervivencia Celular/efectos de los fármacos , Cuscuta/química , Teoría Cuántica , Especies Reactivas de Oxígeno/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Línea Celular Tumoral , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Relación Estructura-ActividadRESUMEN
Cathepsin C (CatC), a key enzyme in neutrophil serine protease activation, is a promising target for treating neutrophilic inflammatory diseases like acute lung injury, ARDS, and COVID-19. Despite its therapeutic potential, no CatC inhibitors are currently available. In this study, a series of gallotannin derivatives were isolated from the traditional Chinese medicine Rhois Galla. Among these, 1,2,3,6-tetra-O-galloyl-ß-d-glucose (1) inhibited CatC with an IC50 of 32.69 ± 2.95 nM. Subsequently, fifteen derivatives of 1 were synthesized and evaluated, revealing key structure-activity relationships. Compound 1 emerged as a potent and selective CatC inhibitor, while a novel synthetic derivative, 15, demonstrated dual inhibitory effects on CatC and cathepsin L. Structural features, including O-galloyl groups at positions 1, 2, and 6 of ß-glucose and a hydrogen donor at position 4, were identified as favorable for CatC inhibition. These findings provide valuable insights for developing novel CatC inhibitors.
Asunto(s)
Catepsina C , Taninos Hidrolizables , Relación Estructura-Actividad , Taninos Hidrolizables/farmacología , Taninos Hidrolizables/síntesis química , Taninos Hidrolizables/química , Humanos , Catepsina C/antagonistas & inhibidores , Catepsina C/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga , PolifenolesRESUMEN
A detailed phytochemical investigation of the traditional Chinese medicine Salvia miltiorrhiza Bunge led to the isolation and idenfication of 22 highly oxygenated abietane diterpenoids, including 17 undescribed compouds (1-10, 15-19, (±)-21) and five known ones. Their structures were elucidated using comprehensive spectroscopic techniques, ECD calculations, and single-crystal X-ray diffraction analysis. Biological screening indicated that these compounds exhibited their anti-inflammatory activity by inhibiting the release of NO, TNF-α, and IL-6, as well as the mRNA expression of pro-inflammatory cytokines and mediators (IL-1ß, IL-6, TNF-α, iNOS, and COX-2) in LPS-induced RAW 264.7 cells. Compounds 4, 5, and 16 exhibited potent inhibotry activity against TNF-α and IL-6 secretion, with IC50 values of 24.47, 0.75, and 3.32 µM against TNF-α, and 2.66, 0.29, and 2.00 µM against IL-6, respectively. Preliminary mechanism study revealed that compounds 4, 5, and 16 could inhibit the NF-κB signaling pathway. These findings suggest that abietane diterpenoids from S. miltiorrhiza are a type of potential anti-inflammatory agent.
Asunto(s)
Abietanos , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Abietanos/farmacología , Abietanos/química , Abietanos/aislamiento & purificación , Ratones , Animales , Células RAW 264.7 , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Descubrimiento de Drogas , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Oxígeno/química , Oxígeno/metabolismo , Citocinas/metabolismo , Citocinas/antagonistas & inhibidoresRESUMEN
Resin glycosides, characteristic of plants of the Convolvulaceae family, are well-known purgative constituents found in traditional medicinal crude drugs, such as Rhizoma Jalapae, Rhizoma Jalapae Braziliensis, Orizaba Jalapa Tuber, and Pharbitidis Semen. The isolated compounds exhibited a wide range of biological activities, including antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug-resistance-modulating properties, as well as cytotoxicity against cancer cells. Ipomoea lacunosa L. (Convolvulaceae) is an herbaceous vine native to the United States. Four new acylated glycosidic acid methyl esters (1-4) and one new glycosidic acid (5) were isolated from the methanol extract of the plant seed. The structures of 1-5 were elucidated using spectroscopic data in conjunction with our previous studies on the components of the crude resin glycoside fraction from I. lacunosa seeds. Compounds 1 and 2 were identified as heptaglycosides, 3 as an octaglycoside, and 4 as a nonaglycoside, all sharing methyl 3S,11S-dihydroxytetradecanoate as a common aglycone. The saccharide moieties were partially acylated by glycosidic acid, 7S-hydroxydecanoic acid 7-O-ß-D-quinovopyranoside, and organic acids, including (E)-2-methylbut-2-enoic, 2S-methylbutyric, and 2R-methyl-3R-hydroxybutyric acids. Compound 5 was identified as a triglycoside with a new aglycone, 4,11-dihydroxyhexadecanoic acid, which is the first glycosidic acid with a hydroxyl group at C-4 of the aglycone moiety.