Search results for "Pharmaceutical Science"
showing 10 items of 2702 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…
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…
Monoclonal antibodies and antibody fragments: state of the art and future perspectives in the treatment of non-haematological tumors
2011
Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies w…
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…
Reduced serum protease activity in Complex Regional Pain Syndrome: The impact of angiotensin-converting enzyme and carboxypeptidases.
2021
Complex Regional Pain Syndrome (CRPS) occurs in about 2% of patients after fracture of the limbs. In an earlier clinical study with 102 probands we have shown that the serum protease network in CRPS might be less effective. Based on these results we hypothesized that angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) activity contribute to the differences of labeled bradykinin (DBK) degradation by patients' sera. Details of the enzymatic processes remained however unclear. The contributions of ACE and CPN in the serum degradation of DBK were studied using specific inhibitors. CPN1-ELISA was performed in serum. It was confirmed that the majority of DBK was degraded by ACE and C…
Different mechanism of relaxation induced by aporphine alkaloids in rat uterus.
1993
Abstract We have examined the uterine relaxant action of three aporphine molecules (S-glaucine, S-boldine and R-apomorphine) in two experimental conditions, with and without calcium in the bathing solution, and compared these effects with those obtained with the calcium antagonists verapamil and diltiazem. The present study shows that the alkaloids relax the uterine muscle but with different mechanisms of action. In Ca2+-containing solution all three alkaloids relaxed the uterus previously contracted by KCl or acetylcholine, but in Ca2+-free medium only R-apomorphine was able to relax oxytocin-induced contraction. The calcium antagonists, verapamil and diltiazem, relaxed KCl- or acetylcholi…
Effects of l-Carnitine in Patients with Autism Spectrum Disorders: Review of Clinical Studies
2019
Carnitine is an amino acid derivative, which plays several important roles in human physiology, in the central nervous system, and for mitochondrial metabolism, in particular. Altered carnitine metabolic routes have been associated with a subgroup of patients with autism spectrum disorders (ASD) and could add to the pathophysiology associated with these disorders. We review the current evidence about the clinical effects of carnitine administration in ASD in both non-syndromic forms and ASD associated with genetic disorders. Two randomized clinical trials and one open-label prospective trial suggest that carnitine administration could be useful for treating symptoms in non-syndromic ASD. Th…
Zinc acexamate inhibits gastric acid and pepsinogen secretion in the rat.
1990
Abstract Pretreatment with zinc acexamate (25–100 mg kg−1 i.p.) inhibited acid and pepsinogen secretion in the pylorus-ligated rat. Zinc acexamate (5–50 mg kg−1 p.o.) also inhibited the increases in acid secretion induced by carbachol (10 μg kg−1) and 2-deoxy-D-glucose (200 mg kg−1) in the perfused stomach of the anaesthetized rat. A delayed antisecretory effect was observed with this drug on histamine induced responses. High concentrations of zinc acexamate (10−5-10−2 M) did not modify the in-vitro activity of pepsin. Administration of zinc acexamate resulted in an increase in the presence of pepsinogen at the mucosal level. A morphological examination of the gastric mucosa confirmed an ac…