RESUMEN
Natural products are one of the important sources for the discovery of new drugs. Betulinic acid (BA), a pentacyclic triterpenoid widely distributed in the plant kingdom, exhibits powerful biological effects, including antitumor activity against various types of cancer cells. A considerable number of BA derivatives have been designed and prepared to remove their disadvantages, such as poor water solubility and low bioavailability. This review summarizes the current studies of the structural diversity of antitumor BA derivatives within the last five years, which provides prospects for further research on the structural modification of betulinic acid.
RESUMEN
Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.
RESUMEN
Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes: ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.
Asunto(s)
Humanos , Inhibidores Enzimáticos , Química , Metabolismo , Frutas , Química , Cinética , Metanol , Química , Simulación del Acoplamiento Molecular , Estructura Molecular , Extractos Vegetales , Química , Unión Proteica , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Metabolismo , Proteínas Tirosina Fosfatasas , Rubus , Química , Relación Estructura-Actividad , Triterpenos , Química , MetabolismoRESUMEN
β2-Adrenoceptor agonists are highly effective bronchodilators and are widely used in the treatment of both chronic obstructive pulmonary disease (COPD) and asthma. In the last 15 years, there has been great interest within the pharmaceutical industry in the discovery of a long β2-adrenoceptor agonist for a mono-therapy or combination therapy. The search for new long-acting β2-adrenoreceptor agonists (LABA's), for the treatment of asthma and COPD, has become a very active area of drug discovery. This article reviews the mechanisms, potential candidates and research advances of long β2-adrenoceptor agonists.
RESUMEN
A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.
Asunto(s)
Animales , Femenino , Ratones , Proliferación Celular , IMP Deshidrogenasa , Metabolismo , Inmunosupresores , Química , Farmacología , Concentración 50 Inhibidora , Ratones Endogámicos BALB C , Ftalazinas , Química , Farmacología , Bazo , Biología Celular , Relación Estructura-Actividad , Linfocitos TRESUMEN
Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.
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Humanos , Antígenos de Neoplasias , Metabolismo , Antineoplásicos , Química , Usos Terapéuticos , Anhidrasa Carbónica IX , Inhibidores de Anhidrasa Carbónica , Química , Usos Terapéuticos , Anhidrasas Carbónicas , Metabolismo , Neoplasias , QuimioterapiaRESUMEN
Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.
Asunto(s)
Humanos , Antineoplásicos , Química , Farmacología , Microtúbulos , Metabolismo , Mitosis , Estructura Molecular , Neoplasias , Quimioterapia , Estilbenos , Química , Farmacología , Relación Estructura-Actividad , Tubulina (Proteína) , Metabolismo , Moduladores de Tubulina , Química , FarmacologíaRESUMEN
<p><b>AIM</b>To establish 3D QSAR model of propenamides with anti-malarial activities.</p><p><b>METHODS</b>Chemical synthesis combined with comparative molecular field analysis (CoMFA).</p><p><b>RESULTS</b>Generated QSAR models for activities of inhibiting chloroquine resistive malaria (W2) and chloroquine sensitive malaria (D6).</p><p><b>CONCLUSION</b>The activity of anti-W2 depends mostly on steric interaction and the activity of anti-D6 depends on both steric and electrostatic interaction.</p>