Search results for "Mechanism of action"
showing 10 items of 229 documents
The In Vitro Interaction of 12-Oxophytodienoic Acid and Related Conjugated Carbonyl Compounds with Thiol Antioxidants
2021
α,β-unsaturated carbonyls interfere with numerous plant physiological processes. One mechanism of action is their reactivity toward thiols of metabolites like cysteine and glutathione (GSH). This work aimed at better understanding these interactions. Both 12-oxophytodienoic acid (12-OPDA) and abscisic acid (ABA) conjugated with cysteine. It was found that the reactivity of α,β-unsaturated carbonyls with GSH followed the sequence trans-2-hexenal <
Photoreceptors and respiratory electron flow involvement in the activity of acifluorfen-methyl and LS 82-556 on nonchlorophyllous soybean cells
1987
Abstract The diphenyl ether acifluorfen-methyl [AFM; methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate] and the pyridine derivative LS 82-556 [( S )-3- N -(methylbenzyl)carbamoyl-5-propionyl-2,6-lutidine] induce light-dependent polyunsaturated fatty acid peroxidation, leading to general membrane disruption. Although devoid of functional chloroplasts, cultured soybean cells are sensitive to AFM and LS 82-556 only in the light. The possible involvement of carotenoids and respiratory electron flow was examined by monitoring ethane evolution, fluorescein release, and dry weight/fresh weight ratio alteration. Herbicide effects on cells exposed to white light or blue light (380–540 n…
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
2020
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…
β(3)‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?
2019
β(3)‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β(3)‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β(3)‐adrenoceptor agonist, are considerably lower than the EC(50) for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β(3)‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression o…
Cardiotoxic Effects of Anti-VEGFR Tyrosine Kinase Inhibitors
2016
Angiogenesis is a key moment in tumor development and proliferation. Until recently oncologists did not know the mechanisms that were behind this phenomenon, but following the discoveries of Folkman and coworkers, they have gradually created and developed a series of drugs that act against angiogenesis by interacting with molecules belonging to the vascular endothelial growth factor (VEGFs) class and its receptors (VEGFRs) giving rise to anticancer effects. Tyrosine kinase inhibitors (TKIs) are a major class of these new anticancer agents, demonstrating high antitumor activity in a variety of "orphan" neoplasms (such as hepatocellular carcinoma, kidney cancer, sarcomas, etc.). The mechanism…
Biological and anticancer properties of Inonotus obliquus extracts
2018
Abstract Inonotus obliquus (IO) has traditionally been used in folk medicine in the treatment of gastrointestinal cancer, cardiovascular disease and diabetes. The aim of our study was to evaluate the biological and metabolic properties of IO extracts. Free radical scavenging properties, inhibition of the activity of xanthine oxidase (XOi), induction of reactive oxygen species (ROS) production, cell viability and expression of superoxide dismutase (SOD1), catalase (CAT) and KI67 mRNA in the human colorectal adenocarcinoma (Caco-2) and normal human skin fibroblast (BJ) cell lines were measured. It was found that 80% ethanol extract of IO exhibited the highest properties inhibiting the activit…
Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody
2016
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable…
Study of novel anticancer 4-thiazolidinone derivatives
2016
Abstract 4-Thiazolidinones are a known class of prospective drug-like molecules, especially in the design of new anticancer agents. Two of the most prominent subtypes of these compounds are 5-ene-2-amino(amino)-4-thiazolidinones and thiopyrano[2,3-d]thiazoles. The latter are considered to be cyclic mimetics of biologically active 5-ene-4-thiazolidinones with similar pharmacological profiles. Therefore, the aim of this study was to evaluate the impact of 4-thiazolidinone-based compounds on cytotoxicity, the apoptotic process, and metabolism in the human squamous carcinoma (SCC-15) cell line. The SCC-15 cells were cultured in phenol red-free DMEM/F12 medium supplemented with 10% FBS, hydrocor…
New insights into the mechanism of action of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives endowed with anticancer potential
2018
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catal…
Abstract C097: Pyrrolo[2′,3′:3,4]cyclohepta[1,2-d][1,2]oxazoles: A new class of antimitotic agents
2019
Abstract Tubulin-binding molecules constitute an important class of antineoplastic agents, with broad activity in both solid and hematologic malignancies. Oxazoles represent the core structure of many drug candidates with multiple targets, providing an attractive scaffold in medicinal chemistry. Diaryl[1,2]oxazoles have emerged as potent analogues of the antitubulin compound combretastatin A-4 (CA-4). Naphtylcombretastin and its derivatives incorporating the isoxazole moiety displayed potent cytotoxic effects and inhibition of tubulin polymerization. In particular, 5-(naphthalen-2-yl)-4-(TMP)-1,2-oxazole and 4-(naphthalen-2-yl)-5-(TMP)-1,2-oxazole showed the same inhibitory potency as napht…