Search results for "medicine.drug_class"
showing 10 items of 2726 documents
Structure, Biosynthesis, and Bioactivity of Photoditritide from Photorhabdus temperata Meg1
2019
A new cyclic peptide photoditritide (1), containing two rare amino acid d-homoarginine residues, was isolated from Photorhabdus temperata Meg1 after the nonribosomal peptide synthetase encoding gene pdtS was activated via promoter exchange. The structure of 1 was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of 1. Bioactivity testing of 1 revealed potent antimicrobial activity against Micrococcus luteus with an MIC value of 3.0 μM and weak antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 13 μM. Additionally, the biosynthetic pathway of 1 was als…
In Vivo Studies on the Anti-Inflammatory Activity of Pachymic and Dehydrotumulosic Acids
2000
Pachymic and dehydrotumulosic acids were studied in different models of acute and chronic inflammation. They proved to be active in most of the methods applied. None of them were active against arachidonic acid-induced ear edema. Dehydrotumulosic acid significantly diminished the mouse ear edema induced by ethyl phenylpropiolate, while pachymic acid was ineffective. When the putative corticoid-like mechanism of both compounds was explored, pachymic acid activity was partially abolished by the glucocorticoid receptor antagonist progesterone, but dehydrotumulosic acid activity was not affected. In vivo experiments demonstrated the inhibition by both principles of the phospholipase A2 (PLA2)-i…
Repurposing of the ALK inhibitor crizotinib for acute leukemia and multiple myeloma cells
2021
Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of ALK-positive non-small-cell lung carcinoma (NSCLC) patients. COMPARE and cluster analyses of transcriptomic data of the NCI cell line panel indicated that genes with different cellular functions regulated the sensitivity or resistance of cancer cells to crizotinib. Transcription factor binding motif analyses in gene promoters divulged two transcription factors possibly regulating the expression of these genes, i.e., RXRA and GATA1, which are important for leukemia and erythroid development, respectively. COMPARE analyses also implied that cell lines of various cancer types displayed varying degr…
Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs
2016
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of …
(+)-Dehydroabietylamine derivatives target triple-negative breast cancer.
2015
Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)…
New hydrogel matrices containing an anti-inflammatory agent. Evaluation of in vitro release and photoprotective activity.
2002
In the present work. the preparation and characterization of hydrogels based on alpha,beta-polyaspartylhydrazide (PAHy) chemically crosslinked with ethyleneglycol diglycidylether (EGDGE) containing Tolmetin sodium salt, are reported. In particular, these samples have been prepared both as water swellable microparticles and as gels at two different crosslinking degrees. The incorporation of Tolmetin sodium salt in PAHy-EGDGE microparticles has been performed after the crosslinking reaction by a soaking procedure or during the formation of the network. The influence of drug loading procedure on Tolmetin release has been evaluated by performing in vitro release study in simulated gastrointesti…
Kaempferol as a dietary anti-inflammatory agent: current therapeutic standing
2020
Inflammation is a physiological response to different pathological, cellular or vascular damages due to physical, chemical or mechanical trauma. It is characterized by pain, redness, heat and swelling. Current natural drugs are carefully chosen as a novel therapeutic strategy for the management of inflammatory diseases. Different phytochemical constituents are present in natural products. These phytochemicals have high efficacy both in vivo and in vitro. Among them, flavonoids occur in many foods, vegetables and herbal medicines and are considered as the most active constituent, having the ability to attenuate inflammation. Kaempferol is a polyphenol that is richly found in fruits, vegetabl…
Demonstration of P29, an oestrogen receptor-associated tumor marker, in human term placenta.
1991
A Mr29,000 serine phosphoprotein (P29) related to oestradiol receptor was studied in human term placenta with the use of a specific monoclonal antibody (D5). D5 was used with two different methods, immunohistochemistry and immunoradiometry. For immunohistochemistry, an indirect immunoperoxidase method was chosen to detect P29 in methacarn-fixed, wax-embedded sections. P29 was mostly confined to the syncytiotrophoblast surrounding placental villi, staining being positive in both cytoplasm and nuclei. The stroma of villi was negative. Content of P29 was uniformly high in crude placental cytosol, as measured by immunoradiometry assays. Specificity of D5 against P29 in placenta was tested by an…
Immunonegative Staining: Epitope Localization on Macromolecules
1996
Relevant literature relating to immunonegative staining is reviewed and integrated with current research of the author and others. The immunonegative staining procedure has been utilized for the study of epitope localization on immune complexes formed from keyhole limpet hemocyanin type 2 (KLH2) di- and multidecamers, and the 20S and 26S proteasome from Xenopus laevis. The IgG linkage pattern of molecules in small immune complexes is considered to provide the most reliable indication of epitope location. For both KLH2 and the 20S proteasome, using domain-specific monoclonal antibodies and a 32-kDa (p32) subunit-specific polyclonal antibody, respectively, it is shown that epitopes (KLH2, sub…
Treatment of pulmonary embolism.
2015
International audience; The treatment of pulmonary embolism is going to be deeply modified by the development of Direct Oral Anticoagulants (DOACs). There are currently three anti-Xa factors (rivaroxaban, apixaban, edoxaban) and one anti-IIa factor (dabigatran) labeled by the FDA and the EMA. All these drugs are direct anticoagulant, orally effective, without the need for adaptation to hemostasis test. As kidney excretion is involved for all of them, they are contra-indicated in patients with severe renal failure (creatinine clearance<30mL/min according to Cockcroft & Gault formula). All the anti-Xa factor drugs are metabolized by liver cytochromes and then contra-indicated in case of liver…