Tricyclic flavonoids with 1,3-dithiolium substructure.
Ontology highlight
ABSTRACT:
SUBMITTER: Bahrin LG
PROVIDER: S-EPMC3511035 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Tricyclic flavonoids with 1,3-dithiolium substructure.
Bahrin Lucian G LG Jones Peter G PG Hopf Henning H
Beilstein journal of organic chemistry 20121116
The synthesis of new 3-dithiocarbamic flavonoids has been accomplished by the reaction of the corresponding 2-hydroxyaryl dithiocarbamates with aminals. These flavonoids were obtained as a mixture of diastereoisomers, the anti isomer being the major one. The heterocyclization of these compounds provided novel tricyclic flavonoids bearing a 1,3-dithiolium-2-yl ring fused at the 3,4-carbon positions of the benzopyran moiety. ...[more]
Similar Datasets
Project description:BACKGROUND:Due to the emergence of multidrug resistant microorganisms, new classes of antibiotics are needed. In this paper, we present the cytotoxic effects of five tricyclic flavonoids, one of which was previously identified as a potent antimicrobial agent. METHODS:All five derivatives were tested against human HOS and MCF7 cancer cell lines using a wound scratch assay. The cytotoxic properties of previously reported flavonoid 4a were also evaluated using the standard MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and live/dead assays, using NHDF, HOS and MCF7 cell lines. RESULTS:All five derivatives were found to inhibit to some degree the proliferation of cancer cells. 4a was also found to be less toxic towards regular versus cancerous human cells. Moreover, the minimum bactericidal concentration of 4a against Staphylococcus aureus was found to be non-toxic for any of the tested human cell lines. CONCLUSIONS:Derivative 4a has the potential of being used as a therapeutic agent against certain microorganisms. Further structure optimization is required for use against tumors.
| S-EPMC6651846 | biostudies-other
Project description:The synthesis of new iodine containing synthetic tricyclic flavonoids is reported. Due to the sensitivity of the precursors to the heat and acidic conditions required for the ring closure of the 1,3-dithiolium core, a new cyclization method has been developed. It consists in the treatment of the corresponding iodine-substituted 3-dithiocarbamic flavonoids with a 1:1 (v/v) mixture of glacial acetic acid-concentrated sulfuric acid at 40 °C. The synthesis of the iodine-substituted 3-dithiocarbamic flavonoids has also been tuned in terms of reaction conditions.
| S-EPMC9740535 | biostudies-literature
Project description:A structure-activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.
| S-EPMC4902053 | biostudies-literature
Project description:MotivationIdentifying the location of binding sites on proteins is of fundamental importance for a wide range of applications, including molecular docking, de novo drug design, structure identification and comparison of functional sites. Here we present Erebus, a web server that searches the entire Protein Data Bank for a given substructure defined by a set of atoms of interest, such as the binding scaffolds for small molecules. The identified substructure contains atoms having the same names, belonging to same amino acids and separated by the same distances (within a given tolerance) as the atoms of the query structure. The accuracy of a match is measured by the root-mean-square deviation or by the normal weight with a given variance. Tests show that our approach can reliably locate rigid binding scaffolds of drugs and metal ions.Availability and implementationWe provide this service through a web server at http://erebus.dokhlab.org.
| S-EPMC3138080 | biostudies-literature
Project description:Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 µM, respectively). The structure-activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 µM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi-Sigma interaction and three Pi-Alkyl interactions.
| S-EPMC6179045 | biostudies-literature
Project description:Judicial structural modifications of 5:7-fused ring-expanded nucleosides (RENs), based on molecular modeling studies with one of its known targets, human RNA helicase (hDDX3), led to the lead, novel, 5:7-5-fused tricyclic heterocycle (1). The latter exhibited promising broad-spectrum in vitro anti-cancer activity against a number of cancer cell lines screened. This paper describes our systematic, albeit limited, structure-activity relationship (SAR) studies on this lead compound, which produced a number of analogs with broad-spectrum in vitro anti-cancer activities against lung, breast, prostate, and ovarian cancer cell lines, in particular compounds 15i, 15j, 15m and 15n which showed IC(50) values in submicromolar to micromolar range, and are worthy of further explorations. The SAR data also enabled us to propose a tentative SAR model for future SAR efforts for ultimate realization of optimally active and minimally toxic anti-cancer compounds based on the diimidazo[4,5-d:4',5'-f][1,3]diazepine structural skeleton of the lead compound 1.
| S-EPMC3546142 | biostudies-literature
Project description:Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs.
2017-03-02 | GSE78853 | GEO
Project description:BACKGROUND:There is an increasing number of proteins with known structure but unknown function. Determining their function would have a significant impact on understanding diseases and designing new therapeutics. However, experimental protein function determination is expensive and very time-consuming. Computational methods can facilitate function determination by identifying proteins that have high structural and chemical similarity. RESULTS:We present LabelHash, a novel algorithm for matching substructural motifs to large collections of protein structures. The algorithm consists of two phases. In the first phase the proteins are preprocessed in a fashion that allows for instant lookup of partial matches to any motif. In the second phase, partial matches for a given motif are expanded to complete matches. The general applicability of the algorithm is demonstrated with three different case studies. First, we show that we can accurately identify members of the enolase superfamily with a single motif. Next, we demonstrate how LabelHash can complement SOIPPA, an algorithm for motif identification and pairwise substructure alignment. Finally, a large collection of Catalytic Site Atlas motifs is used to benchmark the performance of the algorithm. LabelHash runs very efficiently in parallel; matching a motif against all proteins in the 95% sequence identity filtered non-redundant Protein Data Bank typically takes no more than a few minutes. The LabelHash algorithm is available through a web server and as a suite of standalone programs at http://labelhash.kavrakilab.org. The output of the LabelHash algorithm can be further analyzed with Chimera through a plugin that we developed for this purpose. CONCLUSIONS:LabelHash is an efficient, versatile algorithm for large-scale substructure matching. When LabelHash is running in parallel, motifs can typically be matched against the entire PDB on the order of minutes. The algorithm is able to identify functional homologs beyond the twilight zone of sequence identity and even beyond fold similarity. The three case studies presented in this paper illustrate the versatility of the algorithm.
| S-EPMC2996407 | biostudies-literature
Project description:Thus far, the application of phase-retrieval methods in crystallography has mainly been aimed at variants of charge flipping or structure-factor flipping. In this work, the relaxed averaged alternating reflections (RAAR) algorithm is applied to determine anomalously scattering substructures from single-wavelength anomalous diffraction (SAD) data of macromolecules. The algorithm has been implemented in a new program, PRASA, and has been shown to significantly outperform charge flipping in determining anomalously scattering substructures on a test sample of 169 SAD data sets with resolutions up to 3.88?Å.
| S-EPMC5947775 | biostudies-literature
Project description:To search for submolecular foldon units, the spontaneous reversible unfolding and refolding of staphylococcal nuclease under native conditions was studied by a kinetic native-state hydrogen exchange (HX) method. As for other proteins, it appears that staphylococcal nuclease is designed as an assembly of well-integrated foldon units that may define steps in its folding pathway and may regulate some other functional properties. The HX results identify 34 amide hydrogens that exchange with solvent hydrogens under native conditions by way of large transient unfolding reactions. The HX data for each hydrogen measure the equilibrium stability (Delta G(HX)) and the kinetic unfolding and refolding rates (k(op) and k(cl)) of the unfolding reaction that exposes it to exchange. These parameters separate the 34 identified residues into three distinct HX groupings. Two correspond to clearly defined structural units in the native protein, termed the blue and red foldons. The remaining HX grouping contains residues, not well separated by their HX parameters alone, that represent two other distinct structural units in the native protein, termed the green and yellow foldons. Among these four sets, a last unfolding foldon (blue) unfolds with a rate constant of 6 x 10(-6) s(-1) and free energy equal to the protein's global stability (10.0 kcal/mol). It represents part of the beta-barrel, including mutually H-bonding residues in the beta 4 and beta 5 strands, a part of the beta 3 strand that H-bonds to beta 5, and residues at the N-terminus of the alpha2 helix that is capped by beta 5. A second foldon (green), which unfolds and refolds more rapidly and at slightly lower free energy, includes residues that define the rest of the native alpha2 helix and its C-terminal cap. A third foldon (yellow) defines the mutually H-bonded beta1-beta2-beta 3 meander, completing the native beta-barrel, plus an adjacent part of the alpha1 helix. A final foldon (red) includes residues on remaining segments that are distant in sequence but nearly adjacent in the native protein. Although the structure of the partially unfolded forms closely mimics the native organization, four residues indicate the presence of some nonnative misfolding interactions. Because the unfolding parameters of many other residues are not determined, it seems likely that the concerted foldon units are more extensive than is shown by the 34 residues actually observed.
| S-EPMC2268249 | biostudies-literature