SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Reaction of diarylphosphinobenzene-2-sulfonic acids with tertially amines, followed by addition of [PdMeCl(cod)], provided anionic methylpalladium(II) complexes with bidentate phosphine-sulfonate ligands, which show high activity for copolymerization of ethylene with methyl acrylate.
In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been used successfully to treat a range of dermatologic disorders, most successfully those characterized by abnormal neutrophil and eosinophil accumulation. This article reviews and updates the chemistry, pharmacokinetics, clinical application, mechanism of action, adverse effects, and drug interactions of dapsone and the sulfones in dermatology.
The C epsilon H proton resonance of His-12 of reduced cysteine S-sulfonated bovine pancreatic ribonuclease A exhibits a nonlinear temperature dependence of the chemical shift in its 1H-NMR spectrum at an apparent pH of 3.0. At temperatures below ca. 35 degrees C, the temperature dependence of the chemical shift of the His-12 C epsilon H resonance is opposite in sign to those of His-48, His-105, and His-119. At temperatures above ca. 35 degrees C, the temperature dependence of the chemical shift of the His-12 C epsilon H resonance is similar to those of the other three His C epsilon H resonances. These data indicate the existence of an equilibrium between locally ordered and locally disordered environments of His-12 in the sulfonated protein at temperatures below ca. 35 degrees C. The ordered and disordered conformations interconvert at a rate that is fast relative to the 1H-NMR chemical shift time scale--i.e., the locally ordered structure has a lifetime of much less than 7 msec. These results demonstrate that short- and medium-range interactions can define short-lived local structures under conditions of temperature and solution composition at which the native protein structure is stable. Furthermore, they demonstrate the utility of reduced derivatives of disulfide-containing proteins as model systems for the identification of local structures that may play a role as early-forming chain-folding initiation structures.
Plasmodium falciparum causes the most severe form of malaria in humans. An important class of drugs in malaria treatment is the sulfone/sulfonamide group, of which sulfadoxine is the most commonly used. The target of sulfadoxine is the enzyme dihydropteroate synthase (DHPS), and sequencing of the DHPS gene has identified amino acid differences that may be involved in the mechanism of resistance to this drug. In this study we have sequenced the DHPS gene in 10 isolates from Thailand and identified a new allele of DHPS that has a previously unidentified amino acid difference. We have expressed eight alleles of P. falciparum PPPK-DHPS in Escherichia coli and purified the functional enzymes to homogeneity. Strikingly, the Ki for sulfadoxine varies by almost three orders of magnitude from 0.14 microM for the DHPS allele from sensitive isolates to 112 microM for an enzyme expressed in a highly resistant isolate. Comparison of the Ki of different sulfonamides and the sulfone dapsone has suggested that the amino acid differences in DHPS would confer cross-resistance to these compounds. These results show that the amino acid differences in the DHPS enzyme of sulfadoxine-resistant isolates of P. falciparum are central to the mechanism of resistance to sulfones and sulfonamides.
Four new sulfonates were prepared as potential inhibitors of antigen 85C, a mycolyl transferase involved in the biosynthesis of the mycobacterial cell wall being designed on the basis of the proposed catalytic mechanism and antigen 85C crystal structure. The inhibitors contained a sulfonate moiety, 3-phenoxybenzyl alcohol or N-(hydroxyethyl)phthalimide as trehalose mimetics, and an alkyl chain of different length mimicking either the mycolate (alpha-chain or the mycolic acid (beta-branch. One compound displayed promising activity in a mycolyltransferase inhibition assay (compound 2b, IC50 = 4.3 microM). The two compounds containing a phthalimide moiety (compounds 3a and 3b) showed significant and selective cytotoxicity against the breast cancer cell line MDA-MB231.
The growth characteristics of influenza virus in an isolated tissue maintained in vitro have been described. When compared with previously reported results using the embryonate egg, a considerably shorter latent period was observed. The release or liberation of the virus occurred throughout a period of many hours. There was no evidence of a general "burst" phenomenon, and the destruction of a cellular membrane did not seem to be essential to or concomitant with the release of virus. An early phase in the development of virus was described which is sensitive to the action of alpha-amino-p-methoxyphenylmethanesulfonic acid and it is by virtue of this that virus multiplication is prevented. If this phase was allowed to go on to completion, replication of virus occurred even in the presence of the sulfonic acid, but the release of virus from the tissue was impaired. It is suggested that the sulfonic acid may interfere with the adsorption or penetration of the virus and that the initiation of infection and the liberation of new virus may be processes which share some common character.
The efficiencies and problems of sulfonation of several condensing reagents for deoxyoligoribonucleotide synthesis have been studied. While 2,4,6-triisopropylbenzenesulfonyl chloride (TPSC1) gave very low yield and slow rate of coupling, the new 1:3 mixture of TPSC1 and tetrazole afforded excellent yield and extremely fast rate of reaction with the lowest rate of sulfonation. The difference and advantages of this mixture over triisopropylbenzenesulfonyl tetrazole (TPSTe) and mesitylenesulfonyl tetrazole (MSTe) are discussed. Mechanisms for the coupling reactions with these condensing reagents to account for the difference in their rates and yields of coupling are discussed.
Propargylic sulfones (PS) are known as pH dependent DNA cleaver. DNA cleavage by PS was considered to proceed by alkylation of G base to allenic sulfones formed from PS in basic condition. We designed PS posessing naphthalene and anthraquinone (AQ) unit and investigated DNA cleavage characteristics. Although these compounds showed high intercalating abilities, this high intercalating ability did not lead to DNA cleaving activity. This result indicates that spatial arrangement of activated allene against guanine base is very important in DNA cleavage by PS. In addition, UV-irradiation to PS possessing AQ unit leads to efficient DNA cleavage at 5'-G of GG sequence. This cleavage pattern exhibited typical cleavage of one-electron oxidation of B-form DNA. Therefore, this result suggests that PS possessing AQ unit cleave DNA by both the alkylation mechanism and the photooxidaization mechanism.
Pseudomonas putida strain DS1 utilizes dimethyl sulfide (DMS) as a sulfur source, and desulfurizes it via dimethyl sulfoxide (DMSO), dimethyl sulfone (DMSO(2)) and methanesulfonate (MSA). Its Tn5 mutant, Dfi74J, no longer utilized DMS, DMSO and DMSO(2), but could oxidize DMS to DMSO(2), suggesting that the conversion of DMSO(2) to MSA was interrupted in the mutant. Sequencing of the Tn5 flanking region of Dfi74J demonstrated that a gene, sfnR (designated for dimethyl sulfone utilization), encoding a transcriptional regulator containing an ATP-dependent sigma(54)-association domain and a DNA-binding domain, was disrupted. sfnR is part of an operon with two other genes, sfnE and sfnC, located immediately upstream of sfnR and in the same orientation. The genes encode NADH-dependent FMN reductase (SfnE) and FMNH(2)-dependent monooxygenase (SfnC). Complementation of Dfi74J with an sfnR-expressing plasmid led to restoration of its growth on DMS, DMSO and DMSO(2). An rpoN-defective mutant of strain DS1, which lacks the sigma(54) factor, grew on MSA, but not on DMS, DMSO and DMSO(2), indicating that SfnR controls expression of gene(s) involved in DMSO(2) metabolism by interaction with sigma(54)-RNA polymerase. Northern hybridization and a reporter gene assay with an sfn-lacZ transcriptional fusion elucidated that expression of the sfnECR operon was induced under sulfate limitation and was dependent on a LysR-type transcriptional regulator, CysB. This is believed to be the first report that a sigma(54)-dependent transcriptional regulator induced under sulfate limitation is involved in sulfur assimilation.
Linear and cyclic analogues of cyclolinopeptide A (CLA) in which one or both phenylalanine residues in fragment Pro6-Pro7-Phe8-Phe9 were substituted by their sulfonated derivatives have been synthesized by SPPS method and cyclization with the BOP reagent. The peptides were examined for their immunosuppressive activity in the humoral and cellular immune response by PFC and DTH tests. All of the analogues retain some immunosuppressive activity of native CLA. Their CD spectra confirm that the optical activity of aromatic residues in CLA depends on their position in the peptide chain. Only the residue in position 8 seems to be optically active. CD spectrum of the cyclic analogue modified in position 9 is very similar to that of native CLA which correlates with its high biological activity. The chiroptical properties of the p-sulfonated Phe-residue are established.
The cellular photosensitivity caused by aluminum phthalocyanines sulfonated to different degrees (AlPcSn) has been investigated. The phototoxic effect increased with decreasing number of sulfonate groups on the macrocycle, with the exception of AlPcS1 which was less phototoxic than AlPcS2 but more phototoxic than AlPcS3 and AlPcS4. The tendency of the AlPcSns to aggregate in our cellular system increased with increasing lipophilicity of the sensitizers. The aggregates had little or no photosensitizing activity. The low efficiency of cell inactivation caused by AlPcS1 can be explained by the highly aggregated state of this sensitizer in the cells. AlPcS2 and AlPcS3 induced a lower degree of cell inactivation per fluorescing quantum and per quantum absorbed by monomeric species than did AlPcS2 and AlPcS1. AlPcS4 and AlPcS3 are therefore suggested to be in different intracellular locations than AlPcS2 and AlPcS1.
We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-benzenesulfonic acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic acid group relative to the amide bond linking the four symmetrically oriented benzenesulfonic acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.
Poly(styrene 4-sulfonate), cellulose sulfate, polymethylenehydroquinone, and PRO 2000 are sulfated or sulfonated polymers (SPs) under development as topical microbicides. They are presumed to work through similar mechanisms of action, although to date there has been no extensive comparison of their anti-human immunodeficiency virus activities. To determine whether any of these candidate microbicides offers a potential advantage, their in vitro activities, mechanisms of action, stabilities in biological secretions, and toxicities were compared. All four compounds were found to be active against X4, R5, and dualtropic primary isolates and against X4 and R5 laboratory-adapted strains in CD4+ T cells, macrophages, and single-coreceptor cell lines. Our single-cycle experiments using pseudotyped virus suggest that all four SPs function at the binding and entry stages of the viral life cycle but differ in degree of postentry effect. Surface plasmon resonance analyses demonstrate that SPs bind to X4 and R5 monomeric glycoprotein 120 with similar high binding affinities. When mixed with cervicovaginal lavage fluid, SPs maintain inhibitory activity at concentrations achievable in formulations.
The molecular interaction of various sulfones and sulfonamides with partially purified dihydropteroate synthetase from Neisseria meningitidis M-166 has been examined. The mode of action of the sulfones was similar to that of the sulfonamides. Both groups of drugs were competitive inhibitors of dihydropteroate synthetase with respect to p-aminobenzoate in a partially purified enzyme preparation. 4,4'-Diaminodiphenylsulfone was three times more effective than sulfadiazine and nine times more effective than sulfanilamide as a competitive inhibitor of dihydropteroate synthetase. The inhibitory activity of 4-amino-4'-acetamidodiphenylsulfone and 4-amino-4'-formamidodiphenylsulfone in this system eliminated their prior conversion to 4,4'-diaminodiphenylsulfone as a requirement for activity.
Two laccase isozymes (I and II) produced by the white-rot fungus Trametes versicolor were purified, and their reactivities towards various substrates and lignins were studied. The N-terminal amino acid sequences of these enzymes were determined and compared to other known laccase sequences. Laccase II showed a very high sequence similarity to a laccase which was previously reported to depolymerize lignin. The reactivities of the two isozymes on most of the substrates tested were similar, but there were some differences in the oxidation rate of polymeric substrates. We found that the two laccases produced similar qualitative effects on kraft lignin and residual lignin in kraft pulp, with no evidence of a marked preference for depolymerization by either enzyme. However, the presence of the mediator 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) prevented and reversed the polymerization of kraft lignin by either laccase. The delignification of hardwood and softwood kraft pulps with the two isozymes and the mediator was compared; either laccase was able to reduce the kappa number of pulp, but only in the presence of 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate).
Pseudomonas sp. HK-1 showed a direct relation between the concentration of alkyl benzene sulfonate (ABS) supplied and cell yields. Since growth on ABS alone did not occur, it was necessary to correlate the total energy obtained by the cells to the ABS concentration when glucose was supplied in a limiting concentration. Several types of metabolic attack in addition to the sulfonate removal were noted: (i) side-chain utilization as indicated by the production of tertiarybutyl alcohol and isopropanol and (ii) ring metabolism as indicated by the presence of phenol, catechol, mandelic acid, benzyl alcohol, and benzoic acid in spent growth media. Utilization of ABS was greatly enhanced by the presence of phenol. This enhancement suggests co-metabolism and that limited concentrations of phenolic products derived from ABS must be accumulated to get active metabolism of the ABS molecule.
An alternative method to defibrinating sheep blood for use in bacteriological media is described. The new procedure incorporates sodium polyanethol sulfonate in a concentration of 0.05% (vol/vol). In testing 117 bacterial and fungal isolates, no significant differences were found with respect to adequate growth, pigment production, hemolytic reactions, and other physical attributes. Further tests demonstrate that the sodium polyanethol sulfonate in sheep blood agar plates does not cause any aberrations in zone sizes around disks used in antibiotic susceptibility tests. Consequently, the method represents a suitable alternative to the use of defibrinated sheep blood in the preparation of bacteriological media.
Fibrinogen adsorptions to surface modified polyurethanes (PU, PU-PEO, and PU-PEO-SO3) were studied from plasma in vitro. PU and PU-PEO surfaces demonstrated that initial adsorption increases with increasing plasma concentration in kinetic profiles and adsorption time in adsorption profiles as a function of plasma concentration, but after the plateau is reached, its adsorption amount decreases as plasma concentration (0.2-2.0%) and adsorption time (1-120 min) increase, respectively. In contrast, PU-PEO-SO3 showed that initial adsorption is almost same regardless of plasma concentration and adsorption time, which is due to the high affinity of surface sulfonate group to fibrinogen. All the surfaces indicated the Vroman effect at about 0.6% plasma concentration; however, the displacement was relatively low. Adsorbed amount of fibrinogen at steady state decreased in the order: PU > PU-PEO-SO3 > PU-PEO, regardless of adsorption time and plasma concentration. The adsorption behavior of PU-PEO-SO3 is attributed to both effect of low binding affinity of PEO chain and high affinity of pendant sulfonate group toward fibrinogen.