Search results for "010404 medicinal & biomolecular chemistry"
showing 10 items of 373 documents
Ruta chalepensis L. (Rutaceae) leaf extract: chemical composition, antioxidant and hypoglicaemic activities.
2017
Ruta chalepensis L. (Rutaceae) leaf extract was investigated for its chemical profile and antioxidant and hypoglycaemic properties. The antioxidant effects were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), Chi-carotene bleaching, and metal chelating activity assays. The carbohydrate-hydrolysing enzymes inhibition assay was used to test the hypoglycaemic potential. R. chalepensis showed a high content of hesperidin and rutin with values of 591.9 and 266.7 mg/g dry extract, respectively. The extract exhibited a promising protection of lipid peroxidation (IC50 value of 16.9 mu g/mL) and inhibited both alpha-amylase and alpha-glucosidase enzymes in a concentration-dependent manner. The…
Comparative chemical composition and bioactivity of leaves essential oils from nine Sicilian accessions of Myrtus communis L.
2019
In this study, the essential oils obtained from the leaves of Myrtus communis L. stored in a collection orchard located at the experimental station ‘Orleans’ of the Department of Agricultural and Forest Sciences of the University of Palermo (Italy) were investigated. The essential oils, analysed by gas chromatography–mass spectrometry, revealed the presence of α-pinene, 1,8-cineole, linalool, limonene and myrtenyl acetate as dominant constituents. The neuroprotective effects of M. communis essential oils were investigated by analysing the antioxidant properties and cholinesterases (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE) inhibitory activity. Essential oils from Scopello…
Discovery of Retinoic Acid-Related Orphan Receptor γt Inverse Agonists via Docking and Negative Image-Based Screening
2018
Retinoic acid-related orphan receptor γt (RORγt) has a vital role in the differentiation of T-helper 17 (TH17) cells. Potent and specific RORγt inverse agonists are sought for treating TH17-related diseases such as psoriasis, rheumatoid arthritis, and type 1 diabetes. Here, the aim was to discover novel RORγt ligands using both standard molecular docking and negative image-based screening. Interestingly, both of these in silico techniques put forward mostly the same compounds for experimental testing. In total, 11 of the 34 molecules purchased for testing were verified as RORγt inverse agonists, thus making the effective hit rate 32%. The pIC50 values for the compounds varied from 4.9 (11 μ…
Synthesis, computational evaluation and pharmacological assessment of acetylsalicylic esters as anti-inflammatory agents
2019
A convenient approach to the synthesis of alkyl esters of aspirin (ASA-OR) has been developed. The synthesis of ASA-OR has been realized in two steps: (1) direct esterification of salicylic acid with alcohols in the presence of dicyclohexylcarbodiimide to give alkyl salicylates (SAL-OR); (2) acetylation of SAL-OR with acetyl chloride to yield ASA-OR. Molecular mechanics simulations, performed to calculate the kinetic radii of several ASA-OR, indicated that the pentyl and hexyl acetylsalicylates possess the best properties to cross cell membranes. The in vitro biological tests demonstrate their anti-inflammatory activity, superimposable to that of aspirin. The results of our study suggest th…
Targeting Orthosteric and Allosteric Pockets of Aromatase via Dual-Mode Novel Azole Inhibitors
2020
[Image: see text] Breast cancer (BC) is the most diffused cancer type in women and the second leading cause of death among the female population. Effective strategies to fight estrogen responsive (ER+) BC, which represents 70% of all BC cases, rely on estrogen deprivation, via the inhibition of the aromatase enzyme, or the modulation of its cognate estrogen receptor. Current clinical therapies significantly increased patient survival time. Nevertheless, the onset of resistance in metastatic BC patients undergoing prolonged treatments is becoming a current clinical challenge, urgently demanding to devise innovative strategies. In this context, here we designed, synthesized, and performed in …
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.
2019
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Exp…
2021
The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-…
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…
Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib
2019
Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…
MYOCARDIAL POTENCY OF AQUEOUS EXTRACT OF HARUNGANA MADAGASCARIENSIS STEM BARK AGAINST ISOPROTERENOL-INDUCED MYOCARDIAL DAMAGE IN RATS
2018
Objectives: The present study was undertaken to evaluate the effects of Harungana madagascariensis on electrocardiographical, biochemical and histopathological changes in isoproterenol (ISO)-induced myocardial infarction in rats. Methods: Male Wistar albino rats were randomly divided and treated with the aqueous extract of Harungana madagascariensis stem bark (AEHM, 200 and 400 mg/kg per os), or normal saline or vitamin E for 7 days with concomitant administration of ISO (85 mg/kg, subcutaneously) on 8th and 9th days, at 24 h interval. Results: The ISO injections to the rats caused cardiac dysfunction evidenced by a marked (P<0.01) elevation in ST-segment, a reduction in R wave amplitude (P…