Search results for "Molecular Medicine"
showing 10 items of 3013 documents
A Mechanistic Approach to theIn VivoAnti-Inflammatory Activity of Sesquiterpenoid Compounds Isolated fromInula viscosa
2001
The present study was designed to examine the anti-inflammatory activity of the sesquiterpenoids ilicic acid and inuviscolide, isolated from Inula viscosa, on cell degranulation, leukotriene biosynthesis, neurogenic drive and glucocorticoid-like interactions. Swiss female mice were used to measure the ear oedema induced by phorbol esters or ethyl phenylpropiolate (EPP), and the paw oedema induced by phospholipase A(2) (PLA(2)) or serotonin. Drug treatment consisted of one topically-applied dose in the ear models and a subcutaneous or intraperitoneal injection in the paw models. Quantitative analysis of leukotriene B(4) (LTB(4)) formation was performed on rat peritoneal neutrophils by high p…
Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum.
2006
We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neut…
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 …
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…
Synthesis, biological evaluation, and structure-activity relationship study of novel cytotoxic aza-caffeic acid derivatives.
2010
Abstract Three series of aza-caffeic acid derivatives with different linkers were designed and synthesized. Each of the synthesized derivatives was then used in cytotoxicity screening on either 8 or 12 human cancer cell lines. The structure–activity relationships on three structural regions A, B, and C are analyzed in detail, indicating that a nine bond linker B, containing a piperazine unit, is the most favorable linker leading to the generation of molecules with potent cytotoxicities. Compound ( E )-1-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-3-(4-(4-ethoxybenzyloxy)-3,5-dimethoxyphenyl)prop-2-en-1-one ( 80 ) exhibited the most significant and selective cytotoxicity to KB, BEL7404, K562, and…
BCR-ABL as a target for novel therapeutic interventions.
2002
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of…
Akute interstitielle Nephritis nach Piperacillin
1989
A 75-year-old woman developed fever, exanthema and nonoliguric renal failure 16 days after the beginning of Piperacillin treatment. Renal biopsy revealed lympho-plasmacellular acute interstitial nephritis (AIN). A lymphocyte-transformation-test showed significant stimulation of patient's lymphocytes by Piperacillin. Corticosteroid-therapy correlated to clinical and renal improvement. Nevertheless the patient died of foudroyant septicemia caused by E. coli. Our report describes the first immunologically documented case of AIN following Piperacillin treatment.