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1.
Drug Des Devel Ther ; 18: 3443-3459, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109327

RESUMO

Purpose: This study aimed to isolate and characterize palmatine from Fibraurea tinctoria Lour stems, quantify its content, and determine its antioxidant and antidiabetic activities. Patients and Methods: Palmatine was isolated from the methanol extract of Fibraurea tinctoria Lour stems by silica gel column chromatography. Structural elucidation of the isolated compounds was performed using spectral data analysis and comparison with the literature. High-Performance Liquid Chromatography (HPLC) was used to quantitatively determine palmatine in the crude methanol extract and fractions. The DPPH and non-enzymatic SOD mimic methods were used to assess the antioxidant activity of the methanol extract, fractions, and isolated compounds. The antidiabetic activity was evaluated in silico by the molecular docking method of alpha-glucosidase and DPP-IV enzymes. Palmatine was used as a test ligand and was compared with berberine and its native ligand or standard compounds. Results: The isolated compound was identified as palmatine. Quantification of palmatine compound by HPLC showed that palmatine was found in the extract and all fractions. In the in vitro antioxidant activity test using the DPPH method, fraction 4 showed the highest activity, with an IC50 value of 91 ppm. In contrast, using the non-enzymatic SOD mimic method, the methanol extract, fraction 5, and isolated compound (palmatine) exhibited very strong antioxidant activity, with IC50 values of 18, 20, and 28 ppm, respectively. The in silico antidiabetic activity of palmatine is thought to have the potential to inhibit these two enzymes. Conclusion: These results showed that Fibraurea tinctoria Lour stems have potential as an antioxidant and antidiabetic agent. Further research on phytochemical and pharmacological is required to validate the use of this plant species for the treatment of various diseases, especially diabetes mellitus.


Assuntos
Antioxidantes , Alcaloides de Berberina , Hipoglicemiantes , Simulação de Acoplamento Molecular , Extratos Vegetais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/química , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/isolamento & purificação , Alcaloides de Berberina/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Picratos/antagonistas & inibidores , Picratos/química , Simulação por Computador , alfa-Glucosidases/metabolismo , Relação Estrutura-Atividade
2.
Biomolecules ; 14(7)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39062496

RESUMO

In this work, the hexane, chloroform, and methanol extracts from Kalanchoe fedtschenkoi were utilized to green-synthesize silver nanoparticles (Kf1-, Kf2-, and Kf3-AgNPs). The Kf1-, Kf2-, and Kf3-AgNPs were characterized by spectroscopy and microscopy techniques. The antibacterial activity of AgNPs was studied against bacteria strains, utilizing the microdilution assay. The DPPH and H2O2 assays were considered to assess the antioxidant activity of AgNPs. The results revealed that Kf1-, Kf2-, and Kf3-AgNPs exhibit an average diameter of 39.9, 111, and 42 nm, respectively. The calculated ζ-potential of Kf1-, Kf2-, and Kf3-AgNPs were -20.5, -10.6, and -7.9 mV, respectively. The UV-vis analysis of the three samples demonstrated characteristic absorption bands within the range of 350-450 nm, which confirmed the formation of AgNPs. The FTIR analysis of AgNPs exhibited a series of bands from 3500 to 750 cm-1, related to the presence of extracts on their surfaces. SEM observations unveiled that Kf1- and Kf2-AgNPs adopted structural arrangements related to nano-popcorns and nanoflowers, whereas Kf3-AgNPs were spherical in shape. It was determined that treatment with Kf1-, Kf2-, and Kf3-AgNPs was demonstrated to inhibit the growth of E. coli, S. aureus, and P. aeruginosa in a dose-dependent manner (50-300 µg/mL). Within the same range, treatment with Kf1-, Kf2-, and Kf3-AgNPs decreased the generation of DPPH (IC50 57.02-2.09 µg/mL) and H2O2 (IC50 3.15-3.45 µg/mL) radicals. This study highlights the importance of using inorganic nanomaterials to improve the biological performance of plant extracts as an efficient nanotechnological approach.


Assuntos
Antibacterianos , Antioxidantes , Química Verde , Kalanchoe , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Prata , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Kalanchoe/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Picratos/antagonistas & inibidores , Picratos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Peróxido de Hidrogênio
3.
Bioorg Chem ; 150: 107601, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38991489

RESUMO

A set of novels 2-thiohydantoin derivatives were synthesized and enaminone function was discussed at position 5 using DMFDMA catalyst which result in formation of pyrazole, isoxazole, benzoxazepine by using reagents such as hydrazine, hydroxylamine and 2-aminothiophenol. These newly synthesized compounds were evaluated for their antioxidant and antiproliferative activity. In vitro studies on the effect of 2-thiohydantoin on scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) confirmed the free radical scavenging and antioxidant activity of 2-thiohydantoin. The synthesized compounds show significant antioxidant activity. The in vitro antitumor activity of 2-thiohydantoin on MCF7 (breast) and PC3 cells (prostate) was evaluated using MTT assay. Some of the synthesized compounds show significant to moderate antiproliferative properties compared to reference drug erlotinib. Among all, compound 4a exhibit potent antitumor properties against MCF7 and PC3 cancer cell lines with IC50 = 2.53 ± 0.09 /ml & with IC50 = 3.25 ± 0.12 µg/ml respectively and has potent antioxidant activity with IC50 = 10.04 ± 0.49 µg/ml.


Assuntos
Antineoplásicos , Antioxidantes , Aromatase , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Simulação de Acoplamento Molecular , Tioidantoínas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Tioidantoínas/farmacologia , Tioidantoínas/química , Tioidantoínas/síntese química , Aromatase/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Catálise , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Termodinâmica , Picratos/antagonistas & inibidores , Hidrazinas , Tioamidas
4.
Bioorg Med Chem Lett ; 110: 129882, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38996937

RESUMO

We present new small-molecular probes targeting the human PD-L1 protein. The molecules were designed by incorporating a newly discovered N-methylmorpholine substituent into a known biphenyl-based structure. Four prototype derivatives of 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carbonitrile (STD4), comprising a morpholine substituent fused with a biphenyl core at different orientations were first verified for their potential binding to PD-L1 using the molecular docking method. A more favorable 7-phenyl derivative of STD4 was then equipped with an amide bond, pyridine, and either a tris(hydroxymethyl)aminomethane or serinol tail leading to two final molecules. Among them, compound 1c showed activity in three bioassays, i.e., the homogenous time-resolved fluorescence (HTRF) assay, immune checkpoint blockade (ICB) assay, and T-cell activation (TCA) assay. Our work shows that morpholine can substitute for dioxane and becomes a promising component in PD-L1-targeting molecules. This finding unlocks new avenues for optimizing PD-L1-targeting compounds, presenting exciting prospects for future developments in this field.


Assuntos
Antígeno B7-H1 , Compostos de Bifenilo , Morfolinas , Receptor de Morte Celular Programada 1 , Humanos , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Relação Estrutura-Atividade , Morfolinas/química , Morfolinas/farmacologia , Morfolinas/síntese química , Estrutura Molecular , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga
5.
Int J Biol Macromol ; 275(Pt 1): 133761, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38987001

RESUMO

This study aimed to enhance the antioxidant activity of carboxymethyl inulin (CMI) by chemical modification. Therefore, a series of cationic Schiff bases bearing heteroatoms were synthesized and incorporated into CMI via ion exchange reactions, ultimately preparing 10 novel CMI derivatives (CMID). Their structures were confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The radical scavenging activities and reducing power of inulin, CMI, and CMID were studied. The results revealed a significant enhancement in antioxidant activity upon the introduction of cationic Schiff bases into CMI. Compared to commercially available antioxidant Vc, CMID demonstrated a broader range of antioxidant activities across the four antioxidant systems analyzed in this research. In particular, CMID containing quinoline (6QSCMI) exhibited the strongest hydroxyl radical scavenging activity, with a scavenging rate of 93.60 % at 1.6 mg mL-1. The CMID bearing imidazole (2MSCMI) was able to scavenge 100 % of the DPPH radical at 1.60 mg mL-1. Furthermore, cytotoxicity experiments showed that the products had good biocompatibility. These results are helpful for evaluating the feasibility of exploiting these products in the food, biomedical, and cosmetics industries.


Assuntos
Antioxidantes , Sequestradores de Radicais Livres , Inulina , Bases de Schiff , Bases de Schiff/química , Inulina/química , Inulina/síntese química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Cátions/química , Radical Hidroxila/química , Humanos , Técnicas de Química Sintética , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Picratos
6.
Phytochemistry ; 225: 114202, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38944099

RESUMO

The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was found to grow vigorously in an intact Pinus koraiensis seed, it is inferred that the strain may develop unique mechanisms associated with the biosynthesis of rare metabolites. Further fermentation of the strain on solid rice medium yielded thirteen undescribed compounds, including three andrastin-type meroterpenoids (1-3), two α-pyrone polyketides (4 and 5), and eight sesquicarane derivatives (6-13), along with seven known compounds (14-20). Their structures were determined by detailed analysis of the spectroscopic and spectrometric data (NMR and HRESIMS), in addition to comparisons of the experimental and calculated ECD data for absolute configurational assignments. The hemiacetal moiety in compounds 1 and 2 and the 3α-hydroxy group in compound 3 were rarely found in the andrastin-type meroterpenoid family. The sesquicaranes belong to a small group of sesquiterpenoid that are rarely reported. Bioassay study showed that compound 1 exhibited inhibitory effects against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 with MIC values of 64 and 32 µg/mL, respectively. In addition, compounds 1 and 3 displayed weak DPPH radical scavenging activities. The andrastins and sesquicaranes in this study enriched the structural diversity of these classes of terpenoids. Of note, this study is the first report on the metabolites of a fungus isolated from P. koraiensis seed.


Assuntos
Testes de Sensibilidade Microbiana , Penicillium , Pinus , Policetídeos , Sementes , Terpenos , Pinus/microbiologia , Pinus/química , Penicillium/química , Sementes/química , Terpenos/química , Terpenos/farmacologia , Terpenos/isolamento & purificação , Policetídeos/química , Policetídeos/farmacologia , Policetídeos/isolamento & purificação , Estrutura Molecular , Pironas/química , Pironas/farmacologia , Pironas/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores
7.
Int J Biol Macromol ; 275(Pt 1): 133214, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897526

RESUMO

The effects of selenium biofortification methods involving sodium selenite and selenium yeast on the structural characteristics, antioxidant activity and binding capacity of Pleurotus eryngii polysaccharides were investigated. Sodium selenite Se-enriched Pleurotus eryngii polysaccharides (Se-SPEP), selenium yeast Se-enriched Pleurotus eryngii polysaccharides (Se-YPEP), and Pleurotus eryngii polysaccharides (PEP) had Se contents of 20.548 ± 1.561, 19.822 ± 0.613, and 0.052 ± 0.016 µg/g, respectively. Compared with PEP, Se-SPEP and Se-YPEP had lower molecular weight and contained the same monosaccharides in varying molar ratios. The results of FT-IR, PS, ZP, and SEM indicated significant alterations in structural characteristics following selenium biofortification. Se-PEPs exhibited superior activity against ABTS, DPPH, and ·OH radicals, as well as the higher binding capacity for Cd2+ and Cu2+ compared to natural polysaccharides. The binding capacity of the polysaccharides for Cd2+ and Cu2+ was higher at pH 6.8 compared to pH 2.0, while the opposite was observed for Pb2+. Furthermore, Se-PEPs exhibited a significantly higher binding capacity for Cd2+ and Cu2+ at both pH levels compared to natural polysaccharides (P < 0.05). Se-YPEP displayed higher antioxidant activity than Se-SPEP, with their binding capacities reversed. These data indicated that selenium biofortification methods have different positive impacts on the structure and activity of polysaccharides compared to natural polysaccharides, making Se-PEPs promising dietary supplements for safeguarding the body against the risks posed by food-derived heavy metals.


Assuntos
Antioxidantes , Biofortificação , Pleurotus , Selênio , Pleurotus/química , Selênio/química , Selênio/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Peso Molecular , Picratos/química , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Polissacarídeos/química , Polissacarídeos/farmacologia , Monossacarídeos/análise , Monossacarídeos/química
8.
Chem Biodivers ; 21(7): e202301816, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38861276

RESUMO

Phytochemical investigation of the methanol extract from the fruits of Macaranga monandra (Euphorbiaceae Muell. et Arg.) afforded one new geranylated 1',2'-dihydrophenanthrene and two new flavonoid derivatives, named macamondrin (1), macamondrione A (2) and B (3) respectively. The structures of these compounds were elucidated mainly by NMR, mass spectral data and in comparison with data from the literature. Along with compounds 1-3, nine known compounds among which oleanolic acid (4); daucosterol (5); 3ß-acetoxy-11α,12α-epoxytaraxerol (6); 3,3',4-tri-O-methylellagic acid (7); 3,3',4,4'-tetra-O-methylellagic acid (8); 4'-O-methyl-6-isoprenylapigenin (9); 4'-O-methyl-8 isoprenylkaempférol (10); 4'-O-methyl-6-isoprénylkaempférol (11); 6-isoprénylkaempférol (12), were also isolated. Crude extracts as well as isolated compounds were evaluated for their antioxidant activity using the ABTS, DPPH and FRAP methods. It appears that the 50 % radical scavenging concentrations ranging from 6.26 to 11.7 µg/ml on the ABTS radical, from 1.77 to 48.22 µg/ml on the DPPH radical, and from 1.54 to 67.97 µg/ml with the FRAP method. For the compounds tested, very good antioxidant activities were observed, which clearly shows that these molecules can have an anti oxidative stress potentiel.


Assuntos
Antioxidantes , Euphorbiaceae , Frutas , Polifenóis , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Frutas/química , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Euphorbiaceae/química , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação
9.
Molecules ; 29(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38893434

RESUMO

Lonicera macranthoides, the main source of traditional Chinese medicine Lonicerae Flos, is extensively cultivated in Southwest China. However, the quality of L. macranthoides produced in this region significantly varies due to its wide distribution and various cultivation breeds. Herein, 50 Lonicerae Flos samples derived from different breeds of L. macranthoides cultivated in Southwest China were collected for quality evaluation. Six organic acids and three saponin compounds were quantitatively analyzed using HPLC. Furthermore, the antioxidant activity of a portion of samples was conducted with 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging experiments. According to the quantitative results, all samples met the quality standards outlined in the Chinese Pharmacopoeia. The samples from Guizhou, whether derived from unopened or open wild-type breeds, exhibited high quality, while the wild-type samples showed relatively significant fluctuation in quality. The samples from Chongqing and Hunan demonstrated similar quality, whereas those from Sichuan exhibited relatively lower quality. These samples demonstrated significant abilities in clearing ABTS and DPPH radicals. The relationship between HPLC chromatograms and antioxidant activity, as elucidated by multivariate analysis, indicated that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C are active components and can serve as Q-markers for quality evaluation.


Assuntos
Antioxidantes , Lonicera , Cromatografia Líquida de Alta Pressão/métodos , Lonicera/química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/análise , China , Picratos/química , Picratos/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Ácidos Sulfônicos/química , Ácidos Sulfônicos/antagonistas & inibidores , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Controle de Qualidade , Benzotiazóis/química , Saponinas/química , Saponinas/análise , Extratos Vegetais
10.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892102

RESUMO

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS•+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 µM).


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Lipoxigenase/metabolismo , Glycine max/enzimologia , Glycine max/química , Inibidores de Lipoxigenase/farmacologia , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Iminas/química , Iminas/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Picratos/química , Picratos/antagonistas & inibidores , Óxidos de Nitrogênio/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/síntese química
11.
Molecules ; 29(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38893290

RESUMO

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki-Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.


Assuntos
Herbicidas , Pirimidinas , Herbicidas/química , Herbicidas/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Acetolactato Sintase/antagonistas & inibidores , Acetolactato Sintase/metabolismo , Acetolactato Sintase/química , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Simulação de Acoplamento Molecular , Plantas Daninhas/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular
12.
Phytochemistry ; 226: 114118, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38692344

RESUMO

Chemical investigation on the leaves of Michelia champaca L. (Magnoliaceae) led to the isolation of five previously undescribed phenylethanoid glycosides (PhGs), 4-O-ß-d-glucopyranosyl-acteoside (1), 4‴-O-(6-O-E-caffeoyl)-ß-d-glucopyranosyl-acteoside (2), 4‴-O-(6-O-E-caffeoyl)-ß-d-glucopyranosyl-isoacteoside (3), 6""-O-E-feruloyl-echinacoside (4), and 6""-O-p-E-coumaroyl-echinacoside (5), together with eighteen known PhGs. Their structures were determined by spectroscopic and chemical methods. All the known PhGs except acteoside (8) were not previously reported in the genus. Twenty-one PhGs exhibited more potent DPPH radical scavenging activity and FRAP than l-ascorbic acid (l-AA), and twenty-two PhGs showed better ABTS radical cation scavenging activity than l-AA. In addition, twelve PhGs displayed more potent cellular reactive oxygen species scavenging activity than curcumin. The results revealed that the leaves of M. champaca are a rich source of phenylethanoid glycosides and antioxidants.


Assuntos
Glicosídeos , Folhas de Planta , Folhas de Planta/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Estrutura Molecular , Compostos de Bifenilo/antagonistas & inibidores , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Picratos/antagonistas & inibidores , Magnoliaceae/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/química , Polifenóis
13.
Molecules ; 29(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792132

RESUMO

In this study, different extraction methods and conditions were used for the extraction of antioxidants from brown macroalgae Fucus spiralis. The extraction methodologies used were ultrasound-assisted extraction (ultrasonic bath and ultrasonic probe), extraction with a vortex, extraction with an Ultra-Turrax® homogenizer, and high-pressure-assisted extraction. The extracts were analyzed for their total phenolic content (TPC) and their antioxidant activity, and evaluated through the 2,2-difenil-1-picrilhidrazil (DPPH) free radical scavenging method and ferric reducing antioxidant power (FRAP) assay. Ultrasonic probe-assisted extraction yielded the highest values of TPC (94.78-474.16 mg gallic acid equivalents/g extract). Regarding the antioxidant activity, vortex-assisted extraction gave the best DPPH results (IC50 1.89-16 µg/mL), while the highest FRAP results were obtained using the Ultra-Turrax® homogenizer (502.16-1188.81 µmol ascorbic acid equivalents/g extract). For each extraction method, response surface methodology was used to analyze the influence of the experimental conditions "extraction time" (t), "biomass/solvent ratio" (R), "solvent" (S, water % in water/ethanol mixture), and "pressure" (P) on TPC, DPPH, and FRAP of the F. spiralis extracts. In general, higher TPC content and higher antioxidant capacity (lower IC50 and higher FRAP) were obtained with higher R, t, and P, and lower S (higher ethanol %). The model regarding the combined effects of independent variables t, R, and S on the FRAP response values for vortex-assisted extractions best fitted the experimental data (R2 0.957), with optimal extraction conditions of t = 300 s, R = 50 g, and S = 25%.


Assuntos
Antioxidantes , Fucus , Fucus/química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/análise , Alga Marinha/química , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Picratos/química , Picratos/antagonistas & inibidores , Solventes/química
14.
Phytochemistry ; 223: 114132, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714288

RESUMO

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives.


Assuntos
Compostos de Bifenilo , Lignanas , Lignanas/química , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Compostos Alílicos , Fenóis
15.
Bioorg Med Chem ; 107: 117762, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38759254

RESUMO

Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 µmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure-activity relationships (SARs) indicated that the introduction of -(4-NO2)Ph, 3-pyridyl, -(2-F)Ph, -(4-F)Ph, -(3-F)Ph, -(4-Cl)Ph, and -(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.


Assuntos
Compostos de Bifenilo , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Lignanas , Proteínas de Sinalização YAP , Humanos , Lignanas/farmacologia , Lignanas/química , Lignanas/síntese química , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Proteínas de Sinalização YAP/metabolismo , Estrutura Molecular , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Sulfetos/química , Sulfetos/farmacologia , Sulfetos/síntese química , Fatores de Transcrição/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/síntese química , Relação Dose-Resposta a Droga , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Compostos Alílicos , Fenóis
16.
Chem Biodivers ; 21(6): e202400379, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38743034

RESUMO

Robusta coffee blossom honey stands as a key regional product in Dak Lak province, Vietnam. Despite its significance, there exists a dearth of scientific data for assessing its quality. This study aims to fill this gap by characterizing the physicochemical properties and biological activities of coffee blossom honeys from three distinct sub-regions within Dak Lak province, Vietnam. These activities include ferric reducing power (FRP), DPPH and ABTS radical scavenging, as well as tyrosinase inhibitory activities. Moreover, the study compares these honey samples with other popular varieties in Vietnam, such as Lychee and Longan honeys. The physicochemical parameters of the honey samples meet the standards set by Codex Alimentarius 2001. Through UPLC analysis, eleven compounds were identified, with caffeine serving as a marker for coffee honey. Furthermore, by employing multiple factor analysis (MFA), it was observed that certain physicochemical properties correlate positively with tyrosinase inhibitory, DPPH, ABTS free radicals scavenging activities, and FRP. Notably, tyrosinase inhibitory activity exhibited a positive correlation with antioxidant activity. These findings underscore the high quality of Coffea robusta honey, showcasing its potent antioxidant and tyrosinase inhibitory activities.


Assuntos
Antioxidantes , Inibidores Enzimáticos , Mel , Monofenol Mono-Oxigenase , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Compostos de Bifenilo/antagonistas & inibidores , Café/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flores/química , Mel/análise , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Picratos/antagonistas & inibidores , Ácidos Sulfônicos/antagonistas & inibidores , Vietnã
17.
Bioorg Chem ; 148: 107433, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754311

RESUMO

Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.


Assuntos
Antagonistas de Receptores de Andrógenos , Antineoplásicos , Benzamidas , Compostos de Bifenilo , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Nitrilas , Feniltioidantoína , Neoplasias da Próstata , Receptores Androgênicos , Humanos , Masculino , Benzamidas/farmacologia , Benzamidas/química , Benzamidas/síntese química , Nitrilas/química , Nitrilas/farmacologia , Feniltioidantoína/farmacologia , Feniltioidantoína/análogos & derivados , Feniltioidantoína/química , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Receptores Androgênicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estrutura Molecular , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/química , Antagonistas de Receptores de Andrógenos/síntese química , Antagonistas de Receptores de Andrógenos/uso terapêutico , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral
18.
J Sep Sci ; 47(9-10): e2300898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726747

RESUMO

Based on the specific binding of drug molecules to cell membrane receptors, a screening and separation method for active compounds of natural products was established by combining phospholipase C (PLC) sensitized hollow fiber microscreening by a solvent seal with high-performance liquid chromatography technology. In the process, the factors affecting the screening were optimized. Under the optimal screening conditions, we screened honokiol (HK), magnolol (MG), negative control drug carbamazepine, and positive control drug amentoflavone, the repeatability of the method was tested. The PLC activity was determined before and after the screening. Experimental results showed that the sensitization factors of PLC of HK and MG were 61.0 and 48.5, respectively, and amentoflavone was 15.0, carbamazepine could not bind to PLC. Moreover, the molecular docking results were consistent with this measurement, indicating that HK and MG could be combined with PLC, and they were potential interacting components with PLC. This method used organic solvent to seal the PLC greatly ensuring the activity, so this method had the advantage of integrating separation, and purification with screening, it not only exhibited good reproducibility and high sensitivity but was also suitable for screening the active components in natural products by various targets in vitro.


Assuntos
Produtos Biológicos , Fosfolipases Tipo C , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/isolamento & purificação , Fosfolipases Tipo C/metabolismo , Fosfolipases Tipo C/química , Fosfolipases Tipo C/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Humanos , Compostos Alílicos , Fenóis
19.
Eur J Med Chem ; 272: 116471, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704945

RESUMO

Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment. This article reviews the latest research on the pharmacological activity of HNK and summarizes the HNK derivatives designed and improved by several researchers. Reviewing these contents could promote the research process of HNK and guide the design of better HNK derivatives for clinical application in the future.


Assuntos
Compostos de Bifenilo , Lignanas , Lignanas/farmacologia , Lignanas/química , Lignanas/síntese química , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Humanos , Relação Estrutura-Atividade , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/síntese química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Compostos Alílicos , Fenóis
20.
Chem Biodivers ; 21(7): e202400660, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771297

RESUMO

The use of plants for medicinal purposes has a long history, however it is desirable a continuous evaluation seeking for complementary scientific evidences for their safe application. Species within the Kalanchoe genus are often referred to as "miracle leaf" due to their remarkable healing properties. Traditionally, these plants have been used to treat infections, inflammation, and cancer. Despite their widespread use, the identification of their active components remains incomplete. This study aimed to differentiate K. crenata (KC), K. marmorata (KM), and K. pinnata (KP) by conducting detailed histochemical and phytochemical analyses, and to assess their antioxidant capabilities. The investigation revealed significant differences between the species, highlighting the variability in phenolic (PC) and flavonoid contents (FC) and their distinct antioxidant effects. The KM demonstrated the greatest results (PC: 59.26±1.53 mgEqGA/g; FC: 12.63±0.91 mgEqCQ/g; DPPH⋅ (IC50): 110.66 ug/mL; ABTS⋅+ (IC50): 26.81 ug/mL; ORAC: 9.65±0.75 mmolTE) when compared to KC and KP. These findings underscore a new reference for research within the Kalanchoe genus.


Assuntos
Antioxidantes , Kalanchoe , Compostos Fitoquímicos , Extratos Vegetais , Kalanchoe/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Fenóis/química , Fenóis/farmacologia , Fenóis/isolamento & purificação , Água/química , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Picratos/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Folhas de Planta/química
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