RESUMO
Rapid separation and enrichment of targets in biological matrixes are of significant interest in multiple life sciences disciplines. Molecularly imprinted polymers (MIPs) have vital applications in extraction and sample cleanup owing to their excellent specificity and selectivity. However, the low mass transfer rate, caused by the heterogeneity of imprinted cavities in polymer networks and strong driving forces, significantly limits its application in high-throughput analysis. Herein, one novel metal affinity-oriented surface imprinting method was proposed to fabricate an MIP with an ultrathin imprinting layer. MIPs were prepared by immobilized template molecules on magnetic nanoparticles (NPs) with metal ions as bridges via coordination, and then polymerization was done. Under the optimized conditions, the thickness of the imprinting layer was merely 1 nm, and the adsorption toward VAL well matched the Langmuir model. Moreover, it took just 5 min to achieve adsorption equilibrium significantly faster than other reported MIPs toward VAL. Adsorption capacity still can reach 25.3 mg/g ascribed to the high imprinting efficiency of the method (the imprinting factor was as high as 5). All evidence proved that recognition sites were all external cavities and were evenly distributed on the surface of the NPs. The obtained MIP NPs exhibited excellent selectivity and specificity toward VAL, with good dispersibility and stability. Coupled with high-performance liquid chromatography, it was successfully used as a dispersed solid phase extraction material to determine VAL in serum. Average recoveries are over 90.0% with relative standard deviations less than 2.14% at three spiked levels (n = 3). All evidence testified that the MIPs fabricated with the proposed method showed a fast trans mass rate and a large rebinding capacity. The method can potentially use high-throughput separation and enrichment of target molecules in batch samples to meet practical applications.
Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Valsartana , Adsorção , Polímeros Molecularmente Impressos/química , Valsartana/química , Propriedades de Superfície , Nanopartículas de Magnetita/química , Cromatografia Líquida de Alta PressãoRESUMO
Furosemide (FUR), banned in sports events by the World Anti-Doping Agency, is a key target in drug tests, necessitating a pretreatment material capable of selectively, rapidly, and sufficiently separating/enriching analytes from complex matrices. Herein, a metal-mediated magnetic molecularly imprinted polymer (mMIP) was rationally designed and synthesized for the specific capture of FUR. The preparations involved the utilization of chromium (III) as the binding pivot, (3-aminopropyl)triethoxysilane as functional monomer, and Fe3O4 as core, all assembled via free radical polymerization. Both the morphologies and adsorptive properties of the mMIP were characterized using multiple methods. The resulting Cr(III)-mediated mMIP (ChM-mMIP) presented excellent selectivity and specificity toward FUR. Under optimized conditions, the adsorption capacity reached 128.50 mg/g within 10 min, and the imprinting factor was 10.41. Moreover, it was also successfully applied as a dispersive solid-phase extraction material, enabling the detection of FUR concentration as low as 20 ng/mL in human urine samples when coupled with a high-performance liquid chromatography/photodiode array. Overall, this study offers a valuable strategy for the development of novel recognition material.
Assuntos
Furosemida , Polímeros Molecularmente Impressos , Humanos , Furosemida/urina , Furosemida/química , Polímeros Molecularmente Impressos/química , Adsorção , Impressão Molecular , Extração em Fase Sólida , Propriedades de Superfície , Cromatografia Líquida de Alta Pressão , Tamanho da Partícula , Dopagem Esportivo/prevenção & controle , Polímeros/química , Polímeros/síntese químicaRESUMO
A series of new N-aryl galantamine analogues (5a-5x) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of N-aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative (5q) (IC50 = 0.19 µM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against H2O2-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of 5q. Derivative 5q would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.
Assuntos
Doença de Alzheimer , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Galantamina/farmacologia , Galantamina/uso terapêutico , Acetilcolinesterase/metabolismo , Paládio , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Catálise , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
A series of novel myrsinane-type Euphorbia diterpene derivatives (1-37) were synthesized from the abundant natural lathyrane-type Euphorbia factor L3, using a multi-step chemical process guided by a bioinspired skeleton conversion strategy, with the aim of discovering potential anti-Alzheimer's disease (AD) bioactive lead compounds. The synthesis process involved a concise reductive olefin coupling reaction through an intramolecular Michael addition with a free radical, followed by a visible-light-triggered regioselective cyclopropane ring-opening. The cholinesterase inhibitory and neuroprotective activities of the synthesized myrsinane derivatives were evaluated. Most of the compounds showed moderate to strong potency, highlighting the importance of ester groups in Euphorbia diterpene. In particular, derivative 37 displayed the most potent acetylcholinesterase (AChE) inhibition, with an IC50 value of 8.3 µM, surpassing that of the positive control, tacrine. Additionally, 37 also showed excellent neuroprotective effect against H2O2-induced injury in SH-SY5Y cells, with a cell viability rate of 124.2% at 50 µM, which was significantly higher than that of the model group (viability rate 52.1%). Molecular docking, reactive oxygen species (ROS) analysis, immunofluorescence, and immunoblotting were performed to investigate the mechanism of action of myrsinane derivative 37. The results indicated that derivative 37 may be a promising myrsinane-type multi-functional lead compound for the treatment of Alzheimer's disease. Furthermore, a preliminary SAR analysis was performed to study the acetylcholinesterase inhibitory and neuroprotective activities of these diterpenes.
Assuntos
Doença de Alzheimer , Diterpenos , Euphorbia , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Euphorbia/química , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio , Doença de Alzheimer/tratamento farmacológico , Diterpenos/química , Esqueleto/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Estrutura Molecular , Relação Estrutura-Atividade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.
Assuntos
Antineoplásicos , Diterpenos , Euphorbia , Humanos , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/farmacologia , Euphorbia/química , Células Hep G2 , Simulação de Acoplamento Molecular , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Therapeutic drug monitoring of captopril, which is a commonly used antihypertensive agent in clinical practice, is necessary. However, matrix effect-induced pretreatment is the bottleneck for determination. Metal-mediated molecularly imprinted polymers, an essential branch of molecularly imprinted polymers with better specificity and selectivity, have been used to separate/enrich analytes from complex matrices. In this work, Cu2+ was introduced to dynamically establish the binding sites of metal-mediated molecularly imprinted polymer towards captopril. All evidence demonstrated that the metal-mediated molecularly imprinted polymer based on Cu2+ coordination obtained a higher adsorption capacity (81.23 mg/g), faster adsorption rate (adsorption equilibrium within 50 min), and better selectivity (with the unrecognized analog). Subsequently, the Cu2+ -mediated molecularly imprinted polymer was used as dispersive molecularly imprinted solid-phase extraction to successfully establish an analytical platform for the determination of trace captopril in rat plasma. The enrichment factor was up to 20, the detection limit was as low as 0.16 µg/ml, and the average recovery was in the range of 87.51%-98.28% with a relative standard deviation of less than 3.29%. This study provides a promising reference for the preparation of selective adsorbents to improve pretreatment.
Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Ratos , Animais , Polímeros/química , Captopril , Extração em Fase Sólida , Adsorção , Fenômenos Magnéticos , Sítios de LigaçãoRESUMO
Four new C20-diterpenoid alkaloids, rotundifosines D-G (1-4), along with eight known ones (5-12) were isolated from the whole plant of Aconitum rotundifolium Kar. & Kir. The structures of the compounds were elucidated on the basis of spectroscopic analyses, including HR-ESI-MS and 1D, 2D NMR. Rotundifosine F (3) is a rare C20-diterpenoid alkaloid with quaternary ammonium salt. Alkaloids 1-4, 5, 6, 9, and 12 were evaluated for cytotoxicity against MCF-7, HCT-116 and HepG2 human cancer cell lines.
Assuntos
Aconitum/química , Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Five new C18-diterpenoid alkaloids, anthriscifoltines C-G (1-5), along with four known diterpenoid alkaloids anthriscifolcines C-F (6-9), were isolated from the extract of Delphinium anthriscifolium var. majus. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). Compounds 1-5 were also evaluated for their cytotoxic activity against MCF-7, HepG2, and H460 human cancer cell lines.
Assuntos
Alcaloides/química , Delphinium/química , Diterpenos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância MagnéticaRESUMO
Twenty-five diterpenoid alkaloids were isolated from the roots of two Aconitum species. The structures of seven new C19-diterpenoid alkaloids, apetaldines A-G (1-7), and 10 known alkaloids (8-17) from Aconitum apetalum and eight known alkaloids (18-25) from Aconitum franchetii var. villosulum were elucidated via HRESIMS, IR, and NMR data. Alkaloids 1-10, 15, 16, and 18-25 were screened for their antifeedant activity. Among the compounds tested, chasmanthinine (19) showed highly potent antifeedant activity with an effective concentration for 50% feeding reduction (EC50) at 0.07 mg/cm2. The antifeedant structure-activity relationship of the diterpenoid alkaloids is also discussed.
Assuntos
Aconitum/química , Alcaloides/química , Alcaloides/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Spodoptera/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Raízes de Plantas/química , Relação Estrutura-AtividadeRESUMO
Five new diterpenoid alkaloids, tianshanitines A-E (1 - 5), along with ten known compounds (6 - 15), were isolated from the EtOH extracts of the whole plant of Delphinium tianshanicum W.T.Wang. Their structures were determined based on extensive spectroscopic analyses, including 1D- and 2D-NMR, HR-ESI-MS, and the structure of tianshanitine C (3) was confirmed by X-ray diffraction analysis. Tianshanitine A (1) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C(1) position. Tianshanitine B (2) is a rare natural diterpenoid alkaloid bearing a OH group at C(16) position. Compounds 1 - 5, 6, 8, 10, 12 and 14 were evaluated for cytotoxicity against HCT116, MCF-7 and HepG2 human cancer cell lines.
Assuntos
Alcaloides/química , Delphinium/química , Diterpenos/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Estrutura Molecular , Análise EspectralRESUMO
A sandwich-type electrochemical immunosensor was proposed for the ultra-sensitive detection of CD44, a potential biomarker for breast cancer. In this design, a customized template-based ionic liquid (1-butyl-2,3-dimethylimidazolium tetrafluoroborate) carbon paste electrode (CILE) served as the sensing platform, and thionine/Au nanoparticles/covalent-organic frameworks (THI/Au/COF) were used as the signal label. Moreover, an enzyme-free signal amplification strategy was introduced by involving H2O2 and phosphotungstate (PW12) with peroxidase-like activity. Under optimized conditions, the linear range is as wide as six orders of magnitude, and the detection limit is as low as 0.71 pg mL-1 (estimated based on S/N = 3). Average recoveries range from 98.16 %-100.1 %, with a relative standard deviation (RSD) of 1.42-8.27 % in mouse serum, and from 98.44 %-99.06 %, with an RSD of 1.14-4.84 % (n = 3) in artificial saliva. Furthermore, the immunosensor exhibits excellent specificity toward CD44, good stability, and low cost, indicating great potential for application in clinical trials.
RESUMO
CDK9 is a cyclin-dependent kinase that plays pivotal roles in multiple cellular functions including gene transcription, cell cycle regulation, DNA damage repair, and cellular differentiation. Targeting CDK9 is considered an attractive strategy for antitumor therapy, especially for leukemia and lymphoma. Several potent small molecule inhibitors, exemplified by TG02 (4), have progressed to clinical trials. However, many of them face challenges such as low clinical efficacy and multiple adverse reactions and may necessitate the exploration of novel strategies to lead to success in the clinic. In this perspective, we present a comprehensive overview of the structural characteristics, biological functions, and preclinical status of CDK9 inhibitors. Our focus extends to various types of inhibitors, including pan-inhibitors, selective inhibitors, dual-target inhibitors, degraders, PPI inhibitors, and natural products. The discussion encompasses chemical structures, structure-activity relationships (SARs), biological activities, selectivity, and therapeutic potential, providing detailed insight into the diverse landscape of CDK9 inhibitors.
Assuntos
Quinase 9 Dependente de Ciclina , Quinases Ciclina-Dependentes , Pontos de Checagem do Ciclo Celular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/químicaRESUMO
AXL, a receptor tyrosine kinase (RTK), plays a pivotal role in various cellular functions. It is primarily involved in processes such as epithelial-mesenchymal transition (EMT) in tumor cells, angiogenesis, apoptosis, immune regulation, and chemotherapy resistance mechanisms. Therefore, targeting AXL is a promising therapeutic approach for the treatment of cancer. AXL inhibitors that have entered clinical trials, such as BGB324(1), have shown promising efficacy in the treatment of melanoma and non-small cell lung cancer. Additionally, novel AXL-targeted drugs, such as AXL degraders, offer a potential solution to overcome the limitations of traditional small-molecule AXL inhibitors targeting single pathways. We provide an overview of the structure and biological functions of AXL, discusses its correlation with various cancers, and critically analyzes the structure-activity relationship of AXL small-molecule inhibitors in cellular contexts. Additionally, we summarize multiple research and development strategies, offering insights for the future development of innovative AXL inhibitors.
Assuntos
Antineoplásicos , Receptor Tirosina Quinase Axl , Descoberta de Drogas , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Humanos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de MedicamentosRESUMO
Ten new nervogenic acid derivatives (1-4, 6-11) and one known compound (5) have been isolated from Liparis nervosa. Their structures were determined using extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 3, 4, 9, 10, and 11 were evaluated for their cytotoxicity against A549, H460, Hela, MCF-7, Caco2, and HepG2 human cancer cell lines.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Orchidaceae/química , Células CACO-2/efeitos dos fármacos , Linhagem Celular Tumoral , Dissacarídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa/efeitos dos fármacos , Hemiterpenos/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Parabenos/químicaRESUMO
Screening bioactive compounds from natural products is one of the most effective ways for new drug research and development. However, obtaining a single extract component on a large scale and with high purity from a complex matrix is still an arduous and challenging task. Herein, one metal mediated magnetic molecularly imprinted polymer (mMIP) was rationally designed and prepared for specifically capturing Aristolochic acid I (AAI). The preparation was done with copper(II) as binding pivot, (3-aminopropyl) triethoxysilane as functional monomer, and Fe3O4 as core, by a one-step sol-gel method. Under the optimized conditions, the apparent maximum binding amount of copper mediated mMIP (Cu-mMIP) reaches as high as 349.72 mg g-1, the highest among the reported AAI-MIPs. Moreover, the nanoparticles exhibit excellent specificity and selectivity, good reproducibility and stability, high superparamagnetism (60.32 emu g-1), and high imprinting efficiency (an imprinting factor of 7). By simulating an industrial-scale separation, 16.56 mg AAI (purity of 95.11%) is obtained after six cycles with 100 mg nanoparticles from 20 g Caulis aristolochiae manshuriensis (Guan-mu-tong). Notably, this takes only 3 hours and consumes 50 mL of methanol. The study provides a potent tool for the green, fast, and specific extraction of high-purity ingredients from natural plants in the manufacturing industry and conventional analysis in the lab.
Assuntos
Aristolochia , Cobre , Polímeros Molecularmente Impressos , Reprodutibilidade dos Testes , Fenômenos MagnéticosRESUMO
Molecular hybridization is a widely employed approach in pharmaceutical chemistry for modifying drugs with the aim of improving pharmacological efficacy and reducing adverse effects. A prime example of this is the case of benorylate, which was created by combining aspirin and acetaminophen, two non-steroidal anti-inflammatory drugs (NSAIDs). Diterpenoid alkaloids, which exhibit potent anti-inflammatory activity, have limitations in their application due to their toxicity and side effects. Thus, we aimed to design new anti-inflammatory lead compounds through the molecular hybridization of the anti-inflammatory active skeletons (lappaconitine, aconorine, and bulleyaconitine A) of diterpenoid alkaloids with classical NSAIDs. In this study, we synthesized 25 diterpenoid alkaloid derivatives with NSAIDs, organized into four series. Among these derivatives, lappaconitine derivative 1e demonstrated the strongest inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells with minimal cytotoxicity. Additionally, 1e effectively suppressed the inflammatory response induced by carrageenan in vivo, with a swelling rate of only 1%. This anti-inflammatory potency was found to be significantly superior to that of naproxen. The molecular docking analysis revealed that the binding affinity of 1e was scored as -10.3 kcal/mol, suggesting that it forms a stable complex with cyclooxygenase-2 (COX-2). Therefore, compound 1e holds potential as a lead anti-inflammatory compound that could be further developed.
Assuntos
Alcaloides , Anti-Inflamatórios não Esteroides , Simulação de Acoplamento Molecular , Estrutura Molecular , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios/farmacologia , Aconitina , Alcaloides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Desenho de FármacosRESUMO
Recently, metal mediated molecularly imprinted polymers (MMIPs) raise extensive attention due to their special adsorption/desorption mechanism. And the metal ion plays a key role both for MMIPs preparation and molecular recognition. But it is still a big question to select one suitable metal ion. To overcome above problem, one computational approach was proposed by calculating interaction energy (ΔE) of ternary complexes (monomer-M2+-template) with GAMESS software at the PBE0 level. Finally Cu(II) was screened from four doubly charged metal ions with different radii. Then Cu mediated MIP was prepared via surface imprinting technique with Fe3O4 as the core in a water system. Subsequently, the adsorption behavior of the MMIP immobilized Cu(II) was investigated in detail. The results indicated the microspheres own excellent specificity and selectivity towards tetracycline (TC), as well as long-term stability and good reproducibility. The apparent maximum binding capacity and the imprinting factor were as high as 163.5 mg g- 1 and 19, respectively. Coupled with HPLC-PDA, the microspheres was successfully used as a dispersed solid phase extraction material to extract trace TC in chicken liver. At three spiking levels, mean recoveries ranged from 89.3% to 97.1% with relative standard deviations less than 4.0% (n = 3). Limits of detection and quantitation were 0.0073 mg kg- 1 and 0.024 mg kg- 1, respectively, which can meet the strict requirement of the regulations stipulated by EU. Moreover, preliminary studies showed the radius of the metal ion and ΔE of the complexes all affect the adsorption capacity, specificity and mass transfer rate of the MMIP.
Assuntos
Impressão Molecular , Polímeros , Adsorção , Antibacterianos , Fenômenos Magnéticos , Impressão Molecular/métodos , Polímeros Molecularmente Impressos , Polímeros/química , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Tetraciclina , Água/químicaRESUMO
Due to the polygenic and heterogeneous nature of the tumorigenesis process, traditional chemotherapy is far from desirable. Fabricating multifunctional nanoplatforms integrating photodynamic effect can synergistically enhance chemotherapy because they can make the cancer cells much sensitive to chemotherapeutics. However, how to assemble different units in nanoplatforms and minimize side effects caused by chemodrugs and photosensitizers (PSs) still needs to be explored. Herein, a nanoplatform CPP/PS-MIP@DOX is developed using a simultaneously covalently conjugated new aggregation-induced emission (AIE) PS and a cell-penetrating peptide (CPP) on the surface of silica-based molecularly imprinted polymer (MIP) nanoparticles, prepared with doxorubicin (DOX) as the template in the water system via a sol-gel technique. CPP/PS-MIP@DOX has good biocompatibility, high DOX-loading ability, promoted cellular uptake, and sustained and pH-sensitive drug release capability. Furthermore, it can efficiently penetrate into tumor tissue, accurately home to, and accumulate at the tumor site. As a result, a better efficacy with lower cytotoxicity is achieved with a smaller dosage of DOX by utilizing either the photodynamic effect or unique characteristics of the MIP. It is the first nanoplatform fabricated by chemically conjugating AIE PSs directly on the surface of the scaffold via the surface-decorated strategy and successfully applied in cancer therapy. This work provides an effective strategy by constructing AIE PS-based cancer nanomedicines with MIPs as scaffolds.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Polímeros Molecularmente Impressos , Fotoquimioterapia/métodos , Doxorrubicina/farmacologiaRESUMO
Kusnezosines A-C (1-3), three C19-diterpenoid alkaloids with a new skeleton which featured an undescribed lactone type D-ring, were isolated from the roots of Aconitum kusnezoffii Reichb. var. gibbiferum. Kusnezosines A-C are the first naturally occurred C19-diterpenoid alkaloids which possessing an unprecedented lactone D ring, this structure was formed by the cleavage of bond between C-15 and C-16 and a successive lactonization. Their structures were established on the basis of comprehensive spectroscopic data analysis. Besides, another 12 known ones were isolated from this plant, analgesic activity tests on the isolated alkaloids were also carried out.
Assuntos
Aconitum/química , Alcaloides/farmacologia , Analgésicos/farmacologia , Diterpenos/farmacologia , Raízes de Plantas/química , Alcaloides/isolamento & purificação , Analgésicos/isolamento & purificação , Animais , China , Diterpenos/isolamento & purificação , Feminino , Masculino , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
Nervosine VII is one of the known saturated pyrrolizidine alkaloids isolated from the plant of Liparis nervosa. This is first study to investigate the antitumor activity of nervosine VII in vitro, and the results indicated that nervosine VII induced autophagy and apoptosis in HCT116 human colorectal cancer cells. Mechanistic studies showed that nervosine VII-induced apoptosis was associated with the intrinsic pathway by the activation of caspase-9, -3 and -7. Autophagy induced by nervosine VII was characteristic with the regulation of autophagic markers including the increase of LC3-II and beclin 1 proteins, and the decrease of p62 protein. Nervosine VII simultaneously induced autophagy and apoptosis by activated MAPKs signaling pathway including JNK, ERK1/2 and p38, suppressing the p53 signaling pathway.