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1.
Isr Med Assoc J ; 23(7): 426-431, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34251125

RESUMO

BACKGROUND: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL). OBJECTIVES: To characterize medication burden during the last hospitalization in children dying from cancer. METHODS: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters. RESULTS: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with "Do not resuscitate" (DNR) orders (P = 0.055). CONCLUSIONS: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias , Cuidados Paliativos , Polimedicação , Esteroides/uso terapêutico , Assistência Terminal , Criança , Procedimentos Clínicos/estatística & dados numéricos , Demografia , Feminino , Pesquisa sobre Serviços de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Masculino , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos
3.
ACS Appl Mater Interfaces ; 13(27): 31514-31526, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34213305

RESUMO

Micro/nanomotors (MNMs), which propel by transforming various forms of energy into kinetic energy, have emerged as promising therapeutic nanosystems in biomedical applications. However, most MNMs used for anticancer treatment are only powered by one engine or provide a single therapeutic strategy. Although double-engined micromotors for synergistic anticancer therapy can achieve more flexible movement and efficient treatment efficacy, their design remains challenging. In this study, we used a facile preparation method to develop enzymatic/magnetic micromotors for synergetic cancer treatment via chemotherapy and starvation therapy (ST), and the size of micromotors can be easily regulated during the synthetic process. The enzymatic reaction of glucose oxidase, which served as the chemical engine, led to self-propulsion using glucose as a fuel and ST via a reduction in the energy available to cancer cells. Moreover, the incorporation of Fe3O4 nanoparticles as a magnetic engine enhanced the kinetic power and provided control over the direction of movement. Inherent pH-responsive drug release behavior was observed owing to the acidic decomposition of drug carriers in the intracellular microenvironment of cancer cells. This system displayed enhanced anticancer efficacy owing to the synergetic therapeutic strategies and increased cellular uptake in a targeted area because of the improved motion behavior provided by the double engines. Therefore, the demonstrated micromotors are promising candidates for anticancer biomedical microsystems.


Assuntos
Glucose Oxidase/metabolismo , Fenômenos Magnéticos , Microtecnologia/métodos , Neoplasias/terapia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia
4.
Int J Nanomedicine ; 16: 4527-4544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276212

RESUMO

Background: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy. Methods: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety. Results: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice. Conclusion: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Derivados de Hidroxietil Amido/química , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/química , Apoptose , Proliferação de Células , Dissulfetos/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias/patologia , Oxirredução , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200284

RESUMO

Aberrant expression of glycosphingolipids is a hallmark of cancer cells and is associated with their malignant properties. Disialylated gangliosides GD2 and GD3 are considered as markers of neuroectoderm origin in tumors, whereas fucosyl-GM1 is expressed in very few normal tissues but overexpressed in a variety of cancers, especially in small cell lung carcinoma. These gangliosides are absent in most normal adult tissues, making them targets of interest in immuno-oncology. Passive and active immunotherapy strategies have been developed, and have shown promising results in clinical trials. In this review, we summarized the current knowledge on GD2, GD3, and fucosyl-GM1 expression in health and cancer, their biosynthesis pathways in the Golgi apparatus, and their biological roles. We described how their overexpression can affect intracellular signaling pathways, increasing the malignant phenotypes of cancer cells, including their metastatic potential and invasiveness. Finally, the different strategies used to target these tumor-associated gangliosides for immunotherapy were discussed, including the use and development of monoclonal antibodies, vaccines, immune system modulators, and immune effector-cell therapy, with a special focus on adoptive cellular therapy with T cells engineered to express chimeric antigen receptors.


Assuntos
Anticorpos Monoclonais/farmacologia , Biomarcadores Tumorais/metabolismo , Glicoesfingolipídeos/antagonistas & inibidores , Glicoesfingolipídeos/metabolismo , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Animais , Glicoesfingolipídeos/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Transdução de Sinais
6.
Int J Nanomedicine ; 16: 4693-4712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267518

RESUMO

Benefiting from the rapid development of nanotechnology, photodynamic therapy (PDT) is arising as a novel non-invasive clinical treatment for specific cancers, which exerts direct efficacy in destroying primary tumors by generating excessive cytotoxic reactive oxygen species (ROS). Notably, PDT-induced cell death is related to T cell-mediated antitumor immune responses through induction of immunogenic cell death (ICD). However, ICD elicited via PDT is not strong enough and is limited by immunosuppressive tumor microenvironment (ITM). Therefore, it is necessary to improve PDT efficacy through enhancing ICD with the combination of synergistic tumor therapies. Herein, the recent progress of nanomaterials-based PDT combined with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy, employing ICD-boosted treatments is reviewed. An outlook about the future application in clinics of nanomaterials-based PDT strategies is also mentioned.


Assuntos
Morte Celular Imunogênica/efeitos dos fármacos , Nanomedicina/métodos , Nanoestruturas , Fotoquimioterapia/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia
7.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199667

RESUMO

Nanoparticles (NPs) with a high atomic number (Z) are promising radiosensitizers for cancer therapy. However, the dependence of their efficacy on irradiation conditions is still unclear. In the present work, 11 different metal and metal oxide NPs (from Cu (ZCu = 29) to Bi2O3 (ZBi = 83)) were studied in terms of their ability to enhance the absorbed dose in combination with 237 X-ray spectra generated at a 30-300 kVp voltage using various filtration systems and anode materials. Among the studied high-Z NP materials, gold was the absolute leader by a dose enhancement factor (DEF; up to 2.51), while HfO2 and Ta2O5 were the most versatile because of the largest high-DEF region in coordinates U (voltage) and Eeff (effective energy). Several impacts of the X-ray spectral composition have been noted, as follows: (1) there are radiation sources that correspond to extremely low DEFs for all of the studied NPs, (2) NPs with a lower Z in some cases can equal or overcome by the DEF value the high-Z NPs, and (3) the change in the X-ray spectrum caused by a beam passing through the matter can significantly affect the DEF. All of these findings indicate the important role of carefully planning radiation exposure in the presence of high-Z NPs.


Assuntos
Cobre/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/radioterapia , Radiossensibilizantes/uso terapêutico , Bismuto/química , Bismuto/uso terapêutico , Cobre/química , Relação Dose-Resposta a Droga , Humanos , Nanopartículas Metálicas/química , Método de Monte Carlo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Óxidos/química , Óxidos/uso terapêutico , Radiossensibilizantes/química , Dosagem Radioterapêutica
8.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198620

RESUMO

The sigma-1 (σ1) receptor is a 'pluripotent chaperone' protein mainly expressed at the mitochondria-endoplasmic reticulum membrane interfaces where it interacts with several client proteins. This feature renders the σ1 receptor an ideal target for the development of multifunctional ligands, whose benefits are now recognized because several pathologies are multifactorial. Indeed, the current therapeutic regimens are based on the administration of different classes of drugs in order to counteract the diverse unbalanced physiological pathways associated with the pathology. Thus, the multi-targeted directed ligand (MTDL) approach, with one molecule that exerts poly-pharmacological actions, may be a winning strategy that overcomes the pharmacokinetic issues linked to the administration of diverse drugs. This review aims to point out the progress in the development of MTDLs directed toward σ1 receptors for the treatment of central nervous system (CNS) and cancer diseases, with a focus on the perspectives that are proper for this strategy. The evidence that some drugs in clinical use unintentionally bind the σ1 protein (as off-target) provides a proof of concept of the potential of this strategy, and it strongly supports the promise that the σ1 receptor holds as a target to be hit in the context of MTDLs for the therapy of multifactorial pathologies.


Assuntos
Receptores sigma/metabolismo , Animais , Humanos , Concentração Inibidora 50 , Ligantes , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Células-Tronco/metabolismo
9.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201298

RESUMO

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to '(re)-educate' TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.


Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Progressão da Doença , Humanos , Neoplasias/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo
10.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201944

RESUMO

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6-MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral/efeitos dos fármacos , Células Hep G2 , Humanos , Azul de Metileno/química , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Compostos de Amônio Quaternário/química
11.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202245

RESUMO

Cancer-based magnetic theranostics has gained significant interest in recent years and can contribute as an influential archetype in the effective treatment of cancer. Owing to their excellent biocompatibility, minute sizes and reactive functional surface groups, magnetic nanoparticles (MNPs) are being explored as potential drug delivery systems. In this study, MgFe2O4 ferrite MNPs were evaluated for their potential to augment the delivery of the anticancer drug doxorubicin (DOX). These MNPs were successfully synthesized by the glycol-thermal method and functionalized with the polymers; chitosan (CHI), polyvinyl alcohol (PVA) and polyethylene glycol (PEG), respectively, as confirmed by Fourier transform infrared (FTIR) spectroscopy. X-ray diffraction (XRD) confirmed the formation of the single-phase cubic spinel structures while vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic properties of all MNPs. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed small, compact structures with good colloidal stability. CHI-MNPs had the highest DOX encapsulation (84.28%), with the PVA-MNPs recording the lowest encapsulation efficiency (59.49%). The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assays conducted in the human embryonic kidney (HEK293), colorectal adenocarcinoma (Caco-2), and breast adenocarcinoma (SKBR-3) cell lines showed that all the drug-free polymerized MNPs promoted cell survival, while the DOX loaded MNPs significantly reduced cell viability in a dose-dependent manner. The DOX-CHI-MNPs possessed superior anticancer activity (<40% cell viability), with approximately 85.86% of the drug released after 72 h in a pH-responsive manner. These MNPs have shown good potential in enhancing drug delivery, thus warranting further optimizations and investigations.


Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanopartículas de Magnetita , Neoplasias/tratamento farmacológico , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Células CACO-2 , Quitosana/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Compostos Férricos/química , Células HEK293 , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Polietilenoglicóis/química , Álcool de Polivinil/química
12.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203543

RESUMO

In this paper, the steady electrically conducting hybrid nanofluid (CuO-Cu/blood) laminar-mixed convection incompressible flow at the stagnation-point with viscous and gyrotactic microorganisms is considered. Additionally, hybrid nanofluid flow over a horizontal porous stretching sheet along with an induced magnetic field and external magnetic field effectsthat can be used in biomedical fields, such as in drug delivery and the flow dynamics of the microcirculatory system. This investigation can also deliver a perfect view about the mass and heat transfer behavior of blood flow in a circulatory system and various hyperthermia treatments such as the treatment of cancer. The simple partial differential equations (PDEs) are converted into a series of dimensional ordinary differential equations (ODEs), which are determined using appropriate similarities variables (HAM). The influence of the suction or injection parameter, mixed convection, Prandtl number, buoyancy ratio parameter, permeability parameter, magnetic parameter, reciprocal magnetic prandtl number, bioconvection Rayleigh number, coupled stress parameter, thermophoretic parameter, Schmidt number, inertial parameter, heat source parameter, and Brownian motion parameter on the concentration, motile microorganisms, velocity, and temperature is outlined, and we study the physical importance of the present problem graphically.


Assuntos
Sistemas de Liberação de Medicamentos , Campos Magnéticos , Nanopartículas de Magnetita , Modelos Biológicos , Neoplasias/tratamento farmacológico , Animais , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/metabolismo
13.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204103

RESUMO

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Animais , Antineoplásicos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Progressão da Doença , Humanos , Microbiota/efeitos dos fármacos , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos
14.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205019

RESUMO

Clinically, different approaches are adopted worldwide for the treatment of cancer, which still ranks second among all causes of death. Immunotherapy for cancer treatment has been the focus of attention in recent years, aiming for an eventual antitumoral effect through the immune system response to cancer cells both prophylactically and therapeutically. The application of nanoparticulate delivery systems for cancer immunotherapy, which is defined as the use of immune system features in cancer treatment, is currently the focus of research. Nanomedicines and nanoparticulate macromolecule delivery for cancer therapy is believed to facilitate selective cytotoxicity based on passive or active targeting to tumors resulting in improved therapeutic efficacy and reduced side effects. Today, with more than 55 different nanomedicines in the market, it is possible to provide more effective cancer diagnosis and treatment by using nanotechnology. Cancer immunotherapy uses the body's immune system to respond to cancer cells; however, this may lead to increased immune response and immunogenicity. Selectivity and targeting to cancer cells and tumors may lead the way to safer immunotherapy and nanotechnology-based delivery approaches that can help achieve the desired success in cancer treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Imunoterapia , Nanopartículas , Neoplasias/imunologia
15.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209621

RESUMO

Silica nanoparticles (SiO2 NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto the SiO2 NPs surfaces. The DOX·HCl loading onto and release from the SiO2 NPs was monitored via UV-VIS and fluorescence spectra. Alternatively, the zeta potential was also used to monitor and evaluate the DOX·HCl loading process. The results showed that nearly 98% of DOX·HCl was effectively loaded onto the SiO2 NPs' surfaces by electrostatic interaction. The pH-dependence of the process wherein DOX·HCl release out of DOX·HCl-SiO2 NPs was investigated as well. For comparison, both the free DOX·HCl molecules and DOX·HCl-SiO2 NPs were used as the labels for cultured cancer cells. Confocal laser scanning microscopy images showed that the DOX·HCl-SiO2 NPs were better delivered to cancer cells which are more acidic than healthy cells. We propose that engineered DOX·HCl-SiO2 systems are good candidates for drug delivery and clinical applications.


Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanopartículas , Neoplasias , Dióxido de Silício , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Células MCF-7 , Microscopia Confocal , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/farmacologia
16.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200139

RESUMO

Aminophenoxazinones are degradation products resulting from the metabolism of different plant species, which comprise a family of natural products well known for their pharmacological activities. This review provides an overview of the pharmacological properties and applications proved by these compounds and their structural derivatives during 2000-2021. The bibliography was selected according to our purpose from the references obtained in a SciFinder database search for the Phx-3 structure (the base molecule of the aminophenoxazinones). Compounds Phx-1 and Phx-3 are among the most studied, especially as anticancer drugs for the treatment of gastric and colon cancer, glioblastoma and melanoma, among others types of relevant cancers. The main information available in the literature about their mechanisms is also described. Similarly, antibacterial, antifungal, antiviral and antiparasitic activities are presented, including species related directly or indirectly to significant diseases. Therefore, we present diverse compounds based on aminophenoxazinones with high potential as drugs, considering their levels of activity and few adverse effects.


Assuntos
Produtos Biológicos/farmacologia , Oxazinas/farmacologia , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Antivirais/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Plantas/química
17.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202711

RESUMO

Cancer is a multifactorial disease that may be tackled by targeting different signaling pathways. Heme oxygenase-1 (HO-1) and sigma receptors (σRs) are both overexpressed in different human cancers, including prostate and brain, contributing to the cancer spreading. In the present study, we investigated whether HO-1 inhibitors and σR ligands, as well a combination of the two, may influence DU145 human prostate and U87MG human glioblastoma cancer cells proliferation. In addition, we synthesized, characterized, and tested a small series of novel hybrid compounds (HO-1/σRs) 1-4 containing the chemical features needed for HO-1 inhibition and σR modulation. Herein, we report for the first time that targeting simultaneously HO-1 and σR proteins may be a good strategy to achieve increased antiproliferative activity against DU145 and U87MG cells, with respect to the mono administration of the parent compounds. The obtained outcomes provide an initial proof of concept useful to further optimize the structure of HO-1/σRs hybrids to develop novel potential anticancer agents.


Assuntos
Antineoplásicos , Inibidores Enzimáticos , Heme Oxigenase-1/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias , Receptores sigma/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Heme Oxigenase-1/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ratos , Receptores sigma/metabolismo
18.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202721

RESUMO

Marine natural products are abundant resources for antioxidants, but the antioxidant property of the soft corals-derived sinularin and dihydrosinularin were unknown. This study aimed to assess antioxidant potential and antiproliferation effects of above compounds on cancer cells, and to investigate the possible relationships between them. Results show that sinularin and dihydrosinularin promptly reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl (•OH), demonstrating a general radical scavenger activity. Sinularin and dihydrosinularin also show an induction for Fe+3-reduction and Fe+2-chelating capacity which both strengthen their antioxidant activities. Importantly, sinularin shows higher antioxidant properties than dihydrosinularin. Moreover, 24 h ATP assays show that sinularin leads to higher antiproliferation of breast, lung, and liver cancer cells than dihydrosinularin. Therefore, the differential antioxidant properties of sinularin and dihydrosinularin may contribute to their differential anti-proliferation of different cancer cells.


Assuntos
Antozoários/química , Antineoplásicos , Antioxidantes , Diterpenos , Compostos Heterocíclicos com 3 Anéis , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
19.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202760

RESUMO

A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).


Assuntos
Abietanos , Anti-Infecciosos , Antineoplásicos Fitogênicos , Bactérias/crescimento & desenvolvimento , Fungos/crescimento & desenvolvimento , Isodon/química , Lactonas , Neoplasias/tratamento farmacológico , Folhas de Planta/química , Células A549 , Abietanos/química , Abietanos/isolamento & purificação , Abietanos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Células HL-60 , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia
20.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204564

RESUMO

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.


Assuntos
Dendrímeros/farmacologia , Nanomedicina/tendências , Fósforo/farmacologia , Animais , Antineoplásicos/uso terapêutico , Antituberculosos/uso terapêutico , Dendrímeros/química , Humanos , Estrutura Molecular , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fósforo/química , Tuberculose/tratamento farmacológico
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