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1.
Curr Med Chem ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38934279

RESUMO

The clinical effectiveness of the available anticancer drugs has been reduced due to the development of drug resistance and serious adverse effects, which have restricted chemotherapy for cancer. Therefore, there is a persistent need for new anticancer medications with reduced side effects. Medical researchers are pursuing various methods to find new, potent, specifically targeted molecules for cancer treatment. Through various techniques, numerous molecules are discovered. However, among them, acridine stands out as a promising heterocycle that has captured the interest of medicinal chemists and acquired significant pharmacological value. The synthetic adaptability of acridine has enabled the creation of numerous derivatives with a wide range of architectural properties, further accelerating this broad spectrum of pharmacological activities. Recent studies have looked at the mechanisms by which acridine and its analogs inhibit tyrosine kinases, topoisomerases, telomerase, and DNA repair interaction. We have compiled our knowledge of acridine compounds for their anticancer activities, mechanisms of action, structure-activity relationship (SAR), and selective, specific activity against different cancer drug targets, as well as in vitro and in vivo anticancer activities of acridine and its analogs from the perspective of cancer drug discovery, in this review.

2.
Biomed Chromatogr ; 38(4): e5825, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38234085

RESUMO

Determining a drug's bioavailability and bioequivalence is important for developing and approving a drug product. The procedure supports applications for generic drug products and novel therapeutic substances, makes important decisions regarding safety and efficacy, and measures a drug's concentration in biological matrices. This study aimed to develop and validate a specific, simple, sensitive, and accurate method using liquid chromatography-tandem mass spectrometry (LC-MS) for measuring bumetanide (BUM) in human plasma. Chromatographic separation was achieved using a Hypurity C18 column (4.6 × 50 mm, 5 µm) under isocratic conditions, and LC-MS detected positive ionization acquisition modes. Protonated precursor to product ion transitions were observed at m/z 365.08 → 240.10 and 370.04 → 244.52 for BUM and internal standard, respectively. The linear range of BUM in plasma samples was 3.490-401.192 ng/mL. The inter-precision value ranged from 1.76% to 4.75%. The inter-accuracy value ranged from 96.46% to 99.95%. The method was adequately validated per the U.S. Food and Drug Administration guidelines, and the results were within permissible bounds. The Cmax and Tmax values were ~53.097 ± 13.537 ng/mL and 1.25 (0.67-5.00) h, respectively. The new approach showed satisfactory results for studying BUM in human plasma with potential use in pharmacokinetic and bioequivalence investigations.


Assuntos
Bumetanida , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Disponibilidade Biológica , Equivalência Terapêutica , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodos
3.
Mini Rev Med Chem ; 23(16): 1653-1677, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824003

RESUMO

Treatment of a wound infection caused by a multidrug-resistant (MDR) bacterium is challenging since traditional medicine is incapable of curing such infections. As a result, there is a critical need to develop wound dressings resistant to MDR bacteria. Over half of diabetic and burn wounds showed clinical symptoms of infection. Diabetes is a metabolic disorder that may have various consequences, including chronic sores, vascular damage, and neuropathy. Microbial infection and oxidative stress to the fibroblast are common causes of slow and ineffective wound healing. Since wound healing and tissue repair are complex cascades of cellular activities, prompt and ordered healing is critical throughout this process. Despite advances in medication development and sophisticated formulations, treating persistent wound infections remains difficult. The drawbacks of administering antibiotics through the digestive system have motivated the development of enhanced therapeutic dressings with antibacterial activity and the application of antibiotics by localized administration. Antimicrobial wound dressings have great promise for reducing infection risk and improving the healing rate of chronic lesions. Most current research in skin tissue engineering focuses on developing threedimensional scaffolds that mimic natural skin's extracellular matrix (ECM). Electrospinning is a wellestablished method for producing nanoscale fibers. It is a simple, cost-effective, reproducible, and efficient process for encapsulating hydrophobic and hydrophilic antimicrobial compounds in synthetic and natural polymeric carriers. This review discusses various nanofibers as novel delivery systems for antimicrobial compounds in chronic wound healing. We will discuss the significant polymers used to make nanofibers, their manufacturing processes, and, most importantly, their antibacterial effectiveness against microorganisms that typically cause chronic wound infections.


Assuntos
Anti-Infecciosos , Diabetes Mellitus , Infecção dos Ferimentos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Anti-Infecciosos/farmacologia , Pele , Cicatrização , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/terapia , Polímeros
4.
Polymers (Basel) ; 14(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36235942

RESUMO

Infections are the primary cause of death from burns and diabetic wounds. The clinical difficulty of treating wound infections with conventional antibiotics has progressively increased and reached a critical level, necessitating a paradigm change for enhanced chronic wound care. The most prevalent bacterium linked with these infections is Staphylococcus aureus, and the advent of community-associated methicillin-resistant Staphylococcus aureus has posed a substantial therapeutic challenge. Most existing wound dressings are ineffective and suffer from constraints such as insufficient antibacterial activity, toxicity, failure to supply enough moisture to the wound, and poor mechanical performance. Using ineffective wound dressings might prolong the healing process of a wound. To meet this requirement, nanoscale scaffolds with their desirable qualities, which include the potential to distribute bioactive agents, a large surface area, enhanced mechanical capabilities, the ability to imitate the extracellular matrix (ECM), and high porosity, have attracted considerable interest. The incorporation of nanoparticles into nanofiber scaffolds constitutes a novel approach to "nanoparticle dressing" that has acquired significant popularity for wound healing. Due to their remarkable antibacterial capabilities, silver nanoparticles are attractive materials for wound healing. This review focuses on the therapeutic applications of nanofiber wound dressings containing Ag-NPs and their potential to revolutionize wound healing.

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