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1.
Curr Pharm Des ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38726783

RESUMO

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

2.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38399404

RESUMO

Drug repurposing is a promising approach that has the potential to revolutionize the drug discovery and development process. By leveraging existing drugs, we can bring new treatments to patients more quickly and affordably. Anti-inflammatory drugs have been shown to target multiple pathways involved in cancer development and progression. This suggests that they may be more effective in treating cancer than drugs that target a single pathway. Cell viability was measured using the MTT assay. The expression of genes related to inflammation (TNFa, IL1b, COX-1, COX-2, and 5-LOX) was measured in HepG2, MCF7, and THLE-2 cells using qPCR. The levels of TNFα, IL1b, COX-1, COX-2, and 5-LOX were also measured in these cells using an ELISA kit. An enzyme binding assay revealed that sulfadiazine expressed weaker inhibitory activity against COX-2 (IC50 = 5.27 µM) in comparison with the COX-2 selective reference inhibitor celecoxib (COX-2 IC50 = 1.94 µM). However, a more balanced inhibitory effect was revealed for sulfadiazine against the COX/LOX pathway with greater affinity towards 5-LOX (IC50 = 19.1 µM) versus COX-1 (IC50 = 18.4 µM) as compared to celecoxib (5-LOX IC50 = 16.7 µM, and COX-1 IC50 = 5.9 µM). MTT assays revealed the IC50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The anti-inflammatory effect of sulfadiazine was also depicted through its effect on the levels of inflammatory markers and inflammation-related genes (TNFα, IL1b, COX-1, COX-2, 5-LOX). Molecular simulation studies revealed key binding interactions that explain the difference in the activity profiles of sulfadiazine compared to celecoxib. The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-37157219

RESUMO

Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids. Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer. However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to a resurgence of interest in the clinical application of its constituents, particularly cannabinoids. This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.

4.
Comb Chem High Throughput Screen ; 25(14): 2372-2386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330658

RESUMO

Myrica esculenta is an important ethnomedicinal plant used in the traditional system of medicine and as an important nutraceutical. Several studies on the plant justify its use in alternative systems of medicine and establish a scientific rationale for its possible therapeutic application. The plant contains a range of biologically active classes of compounds, particularly diarylheptanoids, flavonoids, terpenes, tannins, and glycosides. The nutraceutical potential of the plant can be particularly attributed to its fruit, and several studies have demonstrated the presence of carbohydrates, proteins, fats, fiber content, and minerals like sodium, potassium, calcium, manganese, iron, copper, and zinc, in it. The current review aims to provide complete insight into the phytochemistry, pharmacological potential, and nutritional potential of the plant, which would not only serve as a comprehensive source of information but also will highlight the scope of isolation and evaluation of these molecules for various disease conditions.


Assuntos
Myrica , Myrica/química , Medicina Tradicional , Frutas , Diarileptanoides , Flavonoides , Extratos Vegetais/farmacologia , Compostos Fitoquímicos/farmacologia
5.
ACS Omega ; 7(38): 34166-34176, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36188256

RESUMO

A series of 27 new quinoxaline derivatives (N-alkyl-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)]acetamides, methyl-2-[2-(3-phenylquinoxalin-2-ylsulfanyl)-acetylamino]alkanoates, and their corresponding dipeptides) were prepared from 3-phenylquinoxaline-2(1H)-thione based on the chemoselective reaction with soft electrophiles. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the efficacy of 27 compounds on cancer cell viability and proliferation. A total of 13 compounds (4a-c, 5, 6, 8c, 9c, 9f, 10a, 10b, 11c, 12b, and 12c) showed inhibitory action on HCT-116 cancer cells and 15 compounds (4a-c, 5, 6, 8c, 9a, 9c, 9f, 9h, 10b, 11c, 12a, 12b, and 12c) showed activity on MCF-7 cancer cells, with compound 10b exhibiting the highest inhibitory action (IC50 1.52 and 2 µg/mL, respectively) on both cell lines. The molecular modeling studies on the human thymidylate synthase (hTS) homodimer interface showed that these compounds are good binders and could selectively inhibit the enzyme by stabilizing its inactive conformation. The study also identified key residues for homodimer binding, which could be used for further optimization and development.

6.
Curr Drug Metab ; 23(9): 735-756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35980054

RESUMO

Epilepsy is a chronic neurological disorder affecting 70 million people globally. One of the fascinating attributes of brain microvasculature is the (BBB), which controls a chain of distinct features that securely regulate the molecules, ions, and cells movement between the blood and the parenchyma. The barrier's integrity is of paramount importance and essential for maintaining brain homeostasis, as it offers both physical and chemical barriers to counter pathogens and xenobiotics. Dysfunction of various transporters in the (BBB), mainly ATP binding cassette (ABC), is considered to play a vital role in hampering the availability of antiepileptic drugs into the brain. ABC (ATP-binding cassette) transporters constitute a most diverse protein superfamily, which plays an essential part in various biological processes, including cell homeostasis, cell signaling, uptake of nutrients, and drug metabolism. Moreover, it plays a crucial role in neuroprotection by out-flowing various internal and external toxic substances from the interior of a cell, thus decreasing their buildup inside the cell. In humans, forty-eight ABC transporters have been acknowledged and categorized into subfamilies A to G based on their phylogenetic analysis. ABC subfamilies B, C, and G, impart a vital role at the BBB in guarding the brain against the entrance of various xenobiotic and their buildup. The illnesses of the central nervous system have received a lot of attention lately Owing to the existence of the BBB, the penetration effectiveness of most CNS medicines into the brain parenchyma is very limited (BBB). In the development of neurological therapies, BBB crossing for medication delivery to the CNS continues to be a major barrier. Nanomaterials with BBB cross ability have indeed been extensively developed for the treatment of CNS diseases due to their advantageous properties. This review will focus on multiple possible factors like inflammation, oxidative stress, uncontrolled recurrent seizures, and genetic polymorphisms that result in the deregulation of ABC transporters in epilepsy and nanotechnology-enabled delivery across BBB in epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Barreira Hematoencefálica/metabolismo , Epilepsia Resistente a Medicamentos/metabolismo , Filogenia , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Nanotecnologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/uso terapêutico
7.
Curr Drug Metab ; 23(10): 781-799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35676850

RESUMO

Breast cancer is the most prevalent cancer in women around the world, having a sudden spread nowadays because of the poor sedentary lifestyle of people. Comprising several subtypes, one of the most dangerous and aggressive ones is triple-negative breast cancer or TNBC. Even though conventional surgical approaches like single and double mastectomy and preventive chemotherapeutic approaches are available, they are not selective to cancer cells and are only for symptomatic treatment. A new branch called nanotechnology has emerged in the last few decades that offers various novel characteristics, such as size in nanometric scale, enhanced adherence to multiple targeting moieties, active and passive targeting, controlled release, and site-specific targeting. Among various nanotherapeutic approaches like dendrimers, lipid-structured nanocarriers, carbon nanotubes, etc., nanoparticle targeted therapeutics can be termed the best among all for their specific cytotoxicity to cancer cells and increased bioavailability to a target site. This review focuses on the types and molecular pathways involving TNBC, existing treatment strategies, various nanotechnological approaches like exosomes, carbon nanotubes, dendrimers, lipid, and carbon-based nanocarriers, and especially various nanoparticles (NPs) like polymeric, photodynamic, peptide conjugated, antibody-conjugated, metallic, inorganic, natural product capped, and CRISPR based nanoparticles already approved for treatment or are under clinical and pre-clinical trials for TNBC.


Assuntos
Dendrímeros , Nanotubos de Carbono , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Dendrímeros/uso terapêutico , Mastectomia , Nanotecnologia , Lipídeos
8.
Anticancer Agents Med Chem ; 22(19): 3291-3303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35702764

RESUMO

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.


Assuntos
Compostos Heterocíclicos , Pirróis , Antibacterianos , Antivirais , Inibidores Enzimáticos , Compostos Heterocíclicos/química , Humanos , Pirróis/química , Pirróis/farmacologia
9.
Anticancer Agents Med Chem ; 22(20): 3343-3369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35593353

RESUMO

Flavonoids, a class of polyphenolic secondary metabolites, are present in fruits, vegetables, beverages such as wine and tea abundantly. Flavonoids exhibit a diverse array of pharmacological activities, including anticancer activity, and are toxic to cancer cells but not harmful to healthy cells. Besides, humans and animals cannot synthesize flavonoids, which leads to a dramatic increase in the consumption of plant flavonoids. Flavonoids consist of a 15- carbon skeleton in C6-C3-C6 rings with divergent substitution patterns to form a series of compounds. Due to their multi-faceted mechanism of action by modulating various signaling pathways associated with apoptosis, cellular proliferation, inflammation, differentiation, metastasis, angiogenesis, they interrupt the initiation, promotion, and progression of cancer. The present review highlights the Structural Activity Relationship (SAR) of flavonoids and recent insights on the progress of natural flavonoids and their synthetic analogs as prospective drug candidates against cancer, along with molecular mechanisms of action.


Assuntos
Flavonoides , Neoplasias , Humanos , Animais , Flavonoides/farmacologia , Flavonoides/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica , Plantas , Carbono , Chá
10.
Anticancer Agents Med Chem ; 22(3): 551-565, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34488596

RESUMO

Cancer is one of the most alarming diseases, with an estimation of 9.6 million deaths in 2018. Glioma occurs in glial cells surrounding nerve cells. The majority of the patients with gliomas have a terminal prognosis, and the ailment has significant sway on patients and their families, be it physical, psychological, or economic wellbeing. As Glioma exhibits, both intra and inter tumour heterogeneity with multidrug resistance and current therapies are ineffective. So the development of safer anti gliomas agents is the need of hour. Bioactive heterocyclic compounds, eithernatural or synthetic, are of potential interest since they have been active against different targets with a wide range of biological activities, including anticancer activities. In addition, they can cross the biological barriers and thus interfere with various signalling pathways to induce cancer cell death. All these advantages make bioactive natural compounds prospective candidates in the management of glioma. In this review, we assessed various bioactive heterocyclic compounds, such as jaceosidin, hispudlin, luteolin, silibinin, cannabidiol, tetrahydrocannabinol, didemnin B, thymoquinone, paclitaxel, doxorubicin, and cucurbitacins for their potential anti-glioma activity. Also, different kinds of chemical reactions to obtain various heterocyclic derivatives, e.g. indole, indazole, benzimidazole, benzoquinone, quinoline, quinazoline, pyrimidine, and triazine, are listed.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Glioma/tratamento farmacológico , Compostos Heterocíclicos/farmacologia , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Neoplasias do Sistema Nervoso Central/patologia , Glioma/patologia , Compostos Heterocíclicos/química , Humanos
11.
Comb Chem High Throughput Screen ; 25(4): 607-615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34225614

RESUMO

BACKGROUND: Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the Blood-Brain Barrier (BBB) impedes the delivery of curcumin to the brain, limiting its therapeutic potential. OBJECTIVE/AIM: This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the bloodbrain barrier. METHODS: The data for the compilation of this review work were searched in PubMed Scopus, Google Scholar, and Science Direct. RESULTS: Various approaches have been opted to expedite the delivery of curcumin across the blood-brain barrier, including liposomes, micelles, polymeric nanoparticles, exosomes, dualtargeting nanoparticles, etc. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.


Assuntos
Curcumina , Doenças Neurodegenerativas , Disponibilidade Biológica , Curcumina/química , Curcumina/farmacologia , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Micelas , Doenças Neurodegenerativas/tratamento farmacológico
12.
CNS Neurol Disord Drug Targets ; 21(10): 940-951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34080970

RESUMO

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in µM), recent patents, and a brief history as neuroprotective agents.


Assuntos
Antineoplásicos , Fármacos Neuroprotetores , Antineoplásicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Nitrogênio , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Relação Estrutura-Atividade
13.
Cancers (Basel) ; 13(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885253

RESUMO

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system's multiple signalling pathways by binding to the 3'-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a 'one drug multiple target' hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

14.
Expert Opin Drug Deliv ; 18(4): 427-448, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33356647

RESUMO

Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Disponibilidade Biológica , Neuropatias Diabéticas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Lipossomos , Polifenóis/farmacologia
15.
Semin Cancer Biol ; 69: 100-108, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31562954

RESUMO

Neuroblastoma (NB) is a widely diagnosed cancer in children, characterized by amplification of the gene encoding the MYCN transcription factor, which is highly predictive of poor clinical outcome and metastatic disease. microRNAs (a class of small non-coding RNAs) are regulated by MYCN transcription factor in neuroblastoma cells. The current research is focussed on identifying differential role of miRNAs and their interactions with signalling proteins, which are intricately linked with cellular processes like apoptosis, proliferation or metastasis. However, the therapeutic success of miRNAs is limited by pharmaco-technical issues which are well counteracted by nanotechnological advancements. The nanoformulated miRNAs unload anti-cancer drugs in a controlled and prespecified manner at target sites, to influence the activity of target protein in amelioration of NB. Recent advances and developments in the field of miRNAs-based systems for clinical management of NBs and the role of nanotechnology to overcome challenges with drug delivery of miRNAs have been reviewed in this paper.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Neuroblastoma/tratamento farmacológico , Animais , Gerenciamento Clínico , Humanos , MicroRNAs/genética , Nanopartículas/química , Neuroblastoma/genética , Neuroblastoma/patologia
16.
Curr Drug Targets ; 22(4): 429-442, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32718288

RESUMO

The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhorts tumors of star-shaped glial cells in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorders like neurofibromatosis and schwannomatosis, which develop the tumor in the nervous system. The management of GBM with chemo-radiotherapy leads to resistance, and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind the failure of drugs are due to DNA alkylation in the cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bioactive compounds from plants referred as phytochemicals, serve as vital sources for anti-cancer drugs. Some prototypical examples include taxol analogs, vinca alkaloids (vincristine, vinblastine), podophyllotoxin analogs, camptothecin, curcumin, aloe-emodin, quercetin, berberine etc. These phytochemicals often regulate diverse molecular pathways, which are implicated in the growth and progression of cancers. However, the challenges posed by the presence of BBB/BBTB to restrict the passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review, we integrated nanotech as a novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Compostos Fitoquímicos , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Humanos , Compostos Fitoquímicos/uso terapêutico
17.
Curr Mol Med ; 21(9): 707-723, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32933459

RESUMO

Exosomes are nano structured (50-90 nm) vesicles that originate from endosomal compartment of eukaryotic cells and are secreted into extracellular matrix. In recent years, there has been increased interest in exploring exosomes for diagnostic and therapeutic applications. Like many other diseases, e.g., neurodegenerative disorders, autoimmune diseases exosomes have a considerable significance in cancer too. Exosomes are known to prevail in large numbers and carry unique cargos in different types of cancers and thus are proving as versatile entities in understanding their biology of cancers and utilized as efficient diagnostic biomarkers in identification of cancer type. In addition to diagnostic applications, there has been an increased interest in recent years to exploit exosomes as carriers for delivery of therapeutic agents to target sites as well. This is indebted to their exceptional non-immunogenic and biomimetic properties that prompted researchers to use exosomes as carriers for delivery of therapeutic agents, e.g., drugs, genes and peptides. Exosomes also circumvent many drawbacks associated with other lipid or polymeric nanocarriers, e.g., low circulation time, lipid toxicities, long term stability, etc. However, in spite of many favorable aspects of exosome based therapy, there have been a number of challenges too. This review will focus on the current status of the exosome based drug therapy for cancer, the challenges faced and its potential for future clinical use.


Assuntos
Exossomos , Neoplasias , Comunicação Celular , Portadores de Fármacos/análise , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico
18.
Semin Cancer Biol ; 69: 391-398, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32302695

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive (WHO grade IV) form of diffuse glioma endowed with tremendous invasive capacity. The availability of narrow therapeutic choices for GBM management adds to the irony, even the post-treatment median survival time is roughly around 14-16 months. Gene mutations seem to be cardinal to GBM formation, owing to involvement of amplified and mutated receptor tyrosine kinase (RTK)-encoding genes, leading to dysregulation of growth factor signaling pathways. Of-late, the role of different microRNAs (miRNAs) in progression and proliferation of GBM was realized, which lead to their burgeon potential applications for diagnostic and therapeutic purposes. miRNA signatures are intricately linked with onset and progression of GBM. Although, progression of GBM causes significant changes in the BBB to form BBTB, but still efficient passage of cancer therapeutics, including antibodies and miRNAs are prevented, leading to low bioavailability. Recent developments in the nanomedicine field provide novel approaches to manage GBM via efficient and brain targeted delivery of miRNAs either alone or as part of cytotoxic pharmaceutical composition, thereby modulating cell signaling in well predicted manner to promise positive therapeutic outcomes.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Glioblastoma/terapia , MicroRNAs/administração & dosagem , Nanomedicina , Nanopartículas/administração & dosagem , Animais , Glioblastoma/genética , Glioblastoma/patologia , Humanos , MicroRNAs/genética , Nanopartículas/química
19.
Comb Chem High Throughput Screen ; 24(10): 1644-1653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33115388

RESUMO

Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds, is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways, prevention of inflammation and oxidative stress, inhibition of angiogenesis and metastasis, and induction of apoptosis, as well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. The proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and downregulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27 and p21, a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induces G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anticancer properties of thymoquinone.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Benzoquinonas/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Nigella sativa/química
20.
Curr Protein Pept Sci ; 21(12): 1218-1222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33023443

RESUMO

Huntington's disease (HD) is a neurodegenerative disease that is genetically inherited through an autosomal dominant gene located on chromosome 4. HD is caused by DNA mutation (generally 37 or more repetition of CAG nucleotides) that leads to an excessive stretch of glutamine residues. However, the main pathogenesis pathway resulted by polyglutamine expansion in mutant HD is unknown. The characteristics of this disease mostly appear in adults. Patients who suffer from this disease have shown an inability to control physical movements, emotional problems, speech disturbance, dementia, loss of thinking ability and death occurs between 15-20 years from the time of symptomatic onset. This review article suggested that investigation of mutation in the HD gene can be done by proteomic analysis such as mass spectroscopy, gel electrophoresis, western blotting, chromatographic based technology, and X-ray crystallography. The primary aim of proteomics is to focus on the molecular changes occurring in HD, there by enhancing the effectiveness of treatment.


Assuntos
Proteína Huntingtina/genética , Doença de Huntington/genética , Proteínas do Tecido Nervoso/genética , Proteômica/métodos , Western Blotting/métodos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Cromatografia/métodos , Cristalografia por Raios X/métodos , Eletroforese em Gel de Poliacrilamida/métodos , Regulação da Expressão Gênica , Humanos , Proteína Huntingtina/metabolismo , Doença de Huntington/tratamento farmacológico , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Mutação , Proteínas do Tecido Nervoso/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Peptídeos/química , Peptídeos/metabolismo , Análise Serial de Proteínas/métodos , Proteômica/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
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