Search results for "Models"
showing 10 items of 8211 documents
Sortase A Inhibitors: Recent Advances and Future Perspectives
2015
Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be com…
Nucleotide's bilinear indices: Novel bio-macromolecular descriptors for bioinformatics studies of nucleic acids. I. Prediction of paromomycin's affin…
2009
A new set of nucleotide-based bio-macromolecular descriptors are presented. This novel approach to bio-macromolecular design from a linear algebra point of view is relevant to nucleic acids quantitative structure-activity relationship (QSAR) studies. These bio-macromolecular indices are based on the calculus of bilinear maps on Re(n)[b(mk)(x (m),y (m)):Re(n) x Re(n)--Re] in canonical basis. Nucleic acid's bilinear indices are calculated from kth power of non-stochastic and stochastic nucleotide's graph-theoretic electronic-contact matrices, M(m)(k) and (s)M(m)(k), respectively. That is to say, the kth non-stochastic and stochastic nucleic acid's bilinear indices are calculated using M(m)(k)…
Styryl-pyrones from Goniothalamus arvensis
1998
Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a known cytotoxic furano-furone, (+)-goniofufurone, have been isolated from the stem bark of Goniothalamus arvensis. A different relative configuration, cis-erythro-erythro for garvensintriol and cis-threo-erythro for etharvendiol, is established, and their absolute stereochemistry is discussed.
Glutamate 270 plays an essential role in K+-activation and domain closure ofThermus thermophilusisopropylmalate dehydrogenase
2014
The mutant E270A of Thermus thermophilus 3-isopropylmalate dehydrogenase exhibits largely reduced (∼1%) catalytic activity and negligible activation by K(+) compared to the wild-type enzyme. A 3-4 kcal/mol increase in the activation energy of the catalysed reaction upon this mutation could also be predicted by QM/MM calculations. In the X-ray structure of the E270A mutant a water molecule was observed to take the place of K(+). SAXS and FRET experiments revealed the essential role of E270 in stabilisation of the active domain-closed conformation of the enzyme. In addition, E270 seems to position K(+) into close proximity of the nicotinamide ring of NAD(+) and the electron-withdrawing effect…
Synthesis and antiproliferative activity of new derivatives containing the polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3’,4’:2,3]azep…
2013
The reaction under reflux between 1-phenyl-3-R-5-methylaminopyrazoles and 2,5-hexanedione lead to 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine derivatives 3b–g. These unusual molecules show the structural complexity of many biologically active natural products and are endowed with the chemical diversity that is required in drug discovery. The compounds 3b,e were reduced by hydrogen in the presence of Palladium on activated charcoal to give the dihydro derivatives 5b,e. Compounds 3b–f and 5b,e were selected by the NCI to evaluate their in vitro antiproliferative activity against 60 human cell lines derived from nine clinically isolated cancer types (leukaemia, lu…
Asymmetric synthesis of α,β-diamino acid derivatives with an aziridine-, azetidine- and γ-lactone-skeleton via Mannich-type additions across α-chloro…
2012
The efficient asymmetric synthesis of new chiral γ-chloro-α,β-diamino acid derivatives via highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycine esters across a chiral α-chloro-N-p-toluenesulfinylimine was developed. The influence of the base, LDA or LiHMDS, used for the formation of the glycine enolates, was of great importance for the anti-/syn-diastereoselectivity of the Mannich-type reaction. The γ-chloro-α,β-diamino acid derivatives proved to be excellent building blocks for ring closure towards optically pure anti- and syn-β,γ-aziridino-α-amino esters, and subsequent ring transformation into trans-3-aminoazetidine-2-carboxylic acid derivatives and α,β-diami…
Interaction of Heparins and Dextran Sulfates with a Mesoscopic Protein Nanopore
2009
A mechanism of how polyanions influence the channel formed by Staphylococcus aureus alpha-hemolysin is described. We demonstrate that the probability of several types of polyanions to block the ion channel depends on the presence of divalent cations and the polyanion molecular weight and concentration. For heparins, a 10-fold increase in molecular weight decreases the half-maximal inhibitory concentration, IC(50), nearly 10(4)-fold. Dextran sulfates were less effective at blocking the channel. The polyanions are significantly more effective at reducing the conductance when added to the trans side of this channel. Lastly, the effectiveness of heparins on the channel conductance correlated wi…
3-acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors.
2000
A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone and 5-acetoxyisogoniothalamin oxide, have been isolated from Goniothalamus arvensis (Annonaceae) stem bark. We report here the isolation and structural elucidation of these compounds with furane-pyrone and styryl-pyrone skeletons, postulating also for the first time their mechanism of cytotoxicity based on inhibition on mammalian mitochondrial respiratory chain.
Application of molecular topology to the prediction of the antimalarial activity of a group of uracil-based acyclic and deoxyuridine compounds.
2008
A topological-mathematical model has been arranged to search for new derivatives of deoxyuridine and related compounds acting as antimalarials against Plasmodium falciparum. By using linear discriminant and multilinear regression analysis a model with two functions was capable to predict adequately the IC(50) for each compound of the training and test series. After carrying out a virtual screening based upon such a model, new structures potentially active against P. falciparum are proposed.