Search results for "molecular structure"
showing 10 items of 1246 documents
Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency.
2018
Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Biological assays were conducted with two cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed that non-aggregating compound 2 showed photoxicity, ascribed to the production of singlet oxygen, being aggregating compound 1 photochemically inactive.…
Pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles, a New Class of Antimitotic Agents Active against Multiple Malignant Cell Types
2020
A new class of pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles was synthesized for the treatment of hyperproliferative pathologies, including neoplasms. The new compounds were screened in the 60 human cancer cell lines of the NCI drug screen and showed potent activity with GI50 values reaching the nanomolar level, with mean graph midpoints of 0.08-0.41 μM. All compounds were further tested on six lymphoma cell lines, and eight showed potent growth inhibitory effects with IC50 values lower than 500 nM. Mechanism of action studies showed the ability of the new [1,2]oxazoles to arrest cells in the G2/M phase in a concentration dependent manner and to induce apoptosis through the mitochondrial…
Noncompetitive agonism at nicotinic acetylcholine receptors; functional significance for CNS signal transduction.
1995
The alkaloids (-)physostigmine (Phy), galanthamine (Gal) and codeine (Cod), and several derivatives and homologous compounds, can act as noncompetitive agonists (NCA) of nicotinic acetylcholine receptors (nAChR) from Torpedo electrocytes, frog and mammalian muscle cells, clonal rat pheochromocytoma cells, cultured hippocampal neurons and several ectopic expression systems, by interacting with a binding site on the alpha-subunits of these nAChRs that is insensitive to the natural transmitter, acetylcholine (ACh), and ACh-competitive agonists and antagonists. Several endogenous ligands, including opioid-type compounds, can also act via this site, albeit at higher concentrations than is typica…
Nicotinic receptor function in the mammalian central nervous system.
1995
The diversity of neuronal nicotinic receptors (nAChRs) in addition to their possible involvement in such pathological conditions as Alzheimer's disease have directed our research towards the characterization of these receptors in various mammalian brain areas. Our studies have relied on electrophysiological, biochemical, and immunofluorescent techniques applied to cultured and acutely dissociated hippocampal neurons, and have been aimed at identifying the various subtypes of nAChRs expressed in the mammalian central nervous system (CNS), at defining the mechanisms by which CNS nAChR activity is modulated, and at determining the ion permeability of CNS nAChR channels. Our findings can be sum…
Computational identification of chemical compounds with potential anti-Chagas activity using a classification tree
2021
Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, was selected to develop the computational model. Dragon software was used to calculate the molecular descriptors and WEKA software to obtain the classification tree. The best model shows accuracy greater than 93.4% for the training set; the tree was also validated using a 10-fold cross-validation p…
Scorpiand-like azamacrocycles prevent the chronic establishment of Trypanosoma cruzi in a murine model.
2013
Chagas disease is today one of the most important neglected diseases for its upcoming expansion to non-endemic areas and has become a threat to blood recipients in many countries. In this study, the trypanocidal activity of ten derivatives of a family of aza-scorpiand like macrocycles is evaluated against Trypanosoma cruzi in vitro and in vivo murine model in which the acute and chronic phases of Chagas disease were analyzed. The compounds 4, 3 and 1 were found to be more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, 4 being the most active compound, particularly in the chronic phase. While all these compounds showed a remarkable degree …
Phenylsulphonyl urenyl chalcone derivatives as dual inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase
2005
Two series of phenylsulphonyl urenyl chalcone derivatives (UCH) with various patterns of substitution were tested for their effects on nitric oxide (NO) and prostaglandin E2 (PGE2) overproduction in RAW 264.7 macrophages. None of the tested compounds reduced NO production more than 50% at 10 microM but most of them inhibited the generation of PGE2 with IC50 values under the micromolar range. Me-UCH 1, Me-UCH 5, Me-UCH 9, Cl-UCH 1, and Cl-UCH 9 were selected to evaluate their influence on human leukocyte functions and eicosanoids generation. These derivatives selectively inhibited cyclo-oxygenase-2 (COX-2) activity in human monocytes being Me-UCH 5 the most potent (IC50 0.06 microM). Selecte…
Synthesis and anti-inflammatory activity of chalcone derivatives
1998
Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.
Cytotoxicity of two naturally occurring flavonoids (dorsmanin F and poinsettifolin B) towards multi-factorial drug-resistant cancer cells.
2015
Abstract Introduction The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy. Methods In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F ( 1 , a flavanone) and poinsettifolin B ( 2 , a chalcone) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry. Results Compounds 1 and…
Cytotoxicity and modes of action of 4'-hydroxy-2',6'-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell…
2014
Abstract Introduction Resistance of cancer to chemotherapy is a main cause in treatment failure. Naturally occurring chalcones possess a wide range of biological activities including anti-cancer effects. In this work, we evaluated the antiproliferative activity of three chalcones [4′-hydroxy-2′,6′-dimethoxychalcone ( 1 ), cardamomin ( 2 ), 2′,4′-dihydroxy-3′,6′-dimethoxychalcone ( 3 )], and four flavanones [( S )-(–)-pinostrobin ( 4 ), ( S )-(–)-onysilin ( 5 ) and alpinetin ( 6 )] toward nine cancer cell lines amongst which were multidrug resistant (MDR) types. Methods The resazurin reduction assay was used to detect the antiproliferative activity of the studied samples whilst flow cytometr…