Search results for "Heterocyclic compound"
showing 10 items of 382 documents
Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains?
2011
International audience; We report the synthesis of two new series of triangular aromatic platforms, either with three aminoalkyl side chains (triazatrinaphthylene series, TrisK: six compounds), or without side chains (triazoniatrinaphthylene, TrisQ). The quadruplex-DNA binding behavior of the two series, which differ essentially by the localization of the cationic charges, was evaluated by means of FRET-melting and G4-FID assays. For the trisubstituted triazatrinaphthylenes (TrisK), the length of the substituents and the presence of terminal hydrogen-bond-donor groups (NH(2)) were shown to be crucial for ensuring a high quadruplex affinity (ΔT(1/2) values of up to 20 °C at 1 μM for the best…
Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study
2012
The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addi…
Ambident PCN Heterocycles: N- and P-Phosphanylation of Lithium 1,3-Benzazaphospholides
2009
Synthetic and structural aspects of the phosphanylation of 1,3-benzazaphospholides 1(Li), ambident benzofused azaphosphacyclopentadienides, are presented. The unusual properties of phospholyl-1,3,2-diazaphospholes inspired us to study the coupling of 1(Li) with chlorodiazaphospholene 2, which led to the N-substituted product 3. Reaction of 1(Li) with chlorodiphenyl- and chlorodicyclohexylphosphane likewise gave N-phosphanylbenzazaphospholes 4 and 5, whereas with the more bulky di-tert-butyl- and di-1-adamantylchlorophosphanes, the diphosphanes 6 and 7 are obtained; in the case of 7 they are isolated as a dimeric LiCl(THF) adduct. Structural information was provided by single-crystal X-ray d…
Cluster organization and pore structure of ion channels formed by beticolin 3, a nonpeptidic fungal toxin
1999
Beticolin 3 (B3) belongs to a family of nonpeptidic phytotoxins produced by the fungus Cercospora beticola, which present a broad spectrum of cytotoxic effects. We report here that, at cytotoxic concentration (10 microM), B3 formed voltage-independent, weakly selective ion channels with multiple conductance levels in planar lipid bilayers. In symmetrical standard solutions, conductance values of the first levels were, respectively, 16 +/- 1 pS, 32 +/- 2 pS, and 57 +/- 2 pS (n = 4) and so on, any conductance level being roughly twice the lower one. Whether a cluster organization of elementary channels or different channel structures underlies this particular property was addressed by investi…
A supramolecular system that strictly follows the binding mechanism of conformational selection
2020
Induced fit and conformational selection are two dominant binding mechanisms in biology. Although induced fit has been widely accepted by supramolecular chemists, conformational selection is rarely studied with synthetic systems. In the present research, we report a macrocyclic host whose binding mechanism is unambiguously assigned to conformational selection. The kinetic and thermodynamic aspects of this system are studied in great detail. It reveals that the kinetic equation commonly used for conformational selection is strictly followed here. In addition, two mathematical models are developed to determine the association constants of the same guest to the two host conformations. A “confo…
Crystal Structure of Perakine Reductase, Founding Member of a Novel Aldo-Keto Reductase (AKR) Subfamily That Undergoes Unique Conformational Changes …
2012
Perakine reductase (PR) catalyzes the NADPH-dependent reduction of the aldehyde perakine to yield the alcohol raucaffrinoline in the biosynthetic pathway of ajmaline in Rauvolfia, a key step in indole alkaloid biosynthesis. Sequence alignment shows that PR is the founder of the new AKR13D subfamily and is designated AKR13D1. The x-ray structure of methylated His(6)-PR was solved to 2.31 Å. However, the active site of PR was blocked by the connected parts of the neighbor symmetric molecule in the crystal. To break the interactions and obtain the enzyme-ligand complexes, the A213W mutant was generated. The atomic structure of His(6)-PR-A213W complex with NADPH was determined at 1.77 Å. Overal…
Development of new Coumarin-based profluorescent substrates for human cytochrome P450 enzymes
2018
Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways.In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3-phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives. Oxidation of profluorescent coumarin derivatives to fluorescent metabolites by 1…
Acquired C1 inhibitor (C1-INH) deficiency type II. Replacement therapy with C1-INH and analysis of patients' C1-INH and anti-C1-INH autoantibodies
1989
Abstract The response of two patients with autoantibody-mediated C1-inhibitor (C1-INH) deficiency to replacement therapy with C1-INH was studied over a period of 3 d. In patient 1 an acute attack of angioedema was successfully managed by infusion of 1,000 U of C1-INH concentrate. C1-INH function returned to normal levels within 30 min, while CH50 and C4 peaked after 6-7 h and C1 hemolytic activity reached 50-60% of normal after 3 d. Immediately after the injection an increase in C1-INH-anti-C1-INH complexes was observed. Based on NH2-terminal sequence analysis of the patients' Mr 96,000 C1-INH, it is concluded that this fragment is generated after cleavage of C1-INH in its active site by on…
Stereoselective Synthesis of Microcarpalide
2002
The first total synthesis of the naturally occurring nonenolide, microcarpalide, is described. The key step in the synthesis was the ring-closing metathesis of a dienic ester prepared in turn by coupling an acid and an alcohol stereoselectively synthesized from (S,S)-tartaric acid and (R)-glycidol, respectively. [structure: see text]
Modulation of drug transport by selected flavonoids: Involvement of P-gp and OCT?
2004
Flavonoids, as a common component of daily nutrition, are a possible source of interference with absorption processes, due to modulation of transporting proteins. In this study, the influence of selected flavonoids (quercetin, isoquercitrin, spiraeoside, rutin, kaempferol, naringenin, naringin, and kaempferol) on the transport of the P-gp substrate [3H]talinolol across Caco-2 cell monolayers was investigated. To elucidate the mechanism behind the interaction observed in this system the potency of the flavonoids to replace [3H]talinolol from its P-gp binding site as well as their activity to inhibit OCT2-mediated [14C]TEA uptake into LLC-PK(1) cells were measured, as P-gp and OCT have been s…