Strong Inhibition of Cholera Toxin B Subunit by Affordable, Polymer-Based Multivalent Inhibitors.

Cholera is a potentially fatal bacterial infection that affects a large number of people in developing countries. It is caused by the cholera toxin (CT), an AB toxin secreted by Vibrio cholera. The toxin comprises a toxic A-subunit and a pentameric B-subunit that bind to the intestinal cell surface.

N-Guanidino Derivatives of 1,5-Dideoxy-1,5-imino-d-xylitol are Potent, Selective, and Stable Inhibitors of β-Glucocerebrosidase.

A series of lipidated guanidino and urea derivatives of 1,5-dideoxy-1,5-imino-d-xylitol were prepared from d-xylose using a concise synthetic protocol. Inhibition assays with a panel of glycosidases revealed that the guanidino analogues display potent inhibition against human recombinant β-glucocerebrosidase with IC values in the low nanomolar range. Related urea analogues of 1,5-dideoxy-1,5-imino-d-xylitol were also synthesized and evaluated in the same fashion and found to be selective for β-galactosidase from bovine liver.

Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques.

Background: Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages in patients, which did however not translate into therapeutic efficacy. This unanticipated finding calls for in-depth screening of drugs intended for targeting plaque macrophages.

Synthesis and evaluation of protein arginine N-methyltransferase inhibitors designed to simultaneously occupy both substrate binding sites.

The protein arginine N-methyltransferases (PRMTs) are a family of enzymes that function by specifically transferring a methyl group from the cofactor S-adenosyl-L-methionine (AdoMet) to the guanidine group of arginine residues in target proteins. The most notable is the PRMT-mediated methylation of arginine residues that are present in histone proteins which can lead to chromatin remodelling and influence gene transcription. A growing body of evidence now implicates dysregulated PRMT activity in a number of diseases including various forms of cancer.

A concise preparation of the fluorescent amino acid L-(7-hydroxycoumarin-4-yl) ethylglycine and extension of its utility in solid phase peptide synthesis.

Incorporation of the unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine (7-HC) is a powerful and reliable approach for the preparation of fluorescently labeled proteins. The growing popularity of this valuable amino acid prompted us to pursue an improved protocol for its synthetic preparation. The optimized procedure here described provides ready access to multi-gram quantities of 7-HC.

Complement-Inhibiting Constituents of Bridelia ferruginea Stem Bark.

A bioassay-guided fractionation of an 80% acetone extract from BRIDELIA FERRUGINEA stem bark showing a dose-dependent inhibitory effect towards both the classical and the alternative pathways of the complement system resulted in the isolation of a biflavanol (gallocatechin-(4'- O-7)-epigallocatechin) ( 1), 3,5-dicaffeoylquinic acid ( 2), 1,3,4,5-tetracaffeoylquinic acid ( 3), and a series of 3-methoxyflavone derivatives, including quercetin 3-methyl ether ( 4), quercetin 3,7,3',4'-tetramethyl ether ( 5), myricetin 3',4',5'-trimethyl ether ( 6; new compound) named ferrugin, myricetin 3,3',4',5'-tetramethyl ether ( 7), myricetin ( 8), and quercetin 3- O-glucoside ( 9) as the active constituents. Especially the biflavanol 1 and the caffeoyl esters of quinic acid 2 and 3 showed a strong inhibitory effect (IC (50) < 10 microM) on the classical pathway, compared to rosmarinic acid. Also on the alternative pathway, the biflavanol 1, the quinic acid derivatives 2 and 3, and some of the 3-methoxyflavones 5, 7 and 8 were more active than rosmarinic acid.

Chalcones from the seed of Cedrelopsis grevei (Ptaeroxylaceae).

The seed of Cedrelopsis grevei (Ptaeroxylaceae) has yielded the known compounds uvangoletin, 5,7-dimethylpinocembrin, cardamonin, flavokawin B, 2'-methoxyhelikrausichalcone, and the novel prenylated chalcones, cedreprenone and cedrediprenone. Cedridiprenone has been shown to exhibit superoxide scavenging properties.

Coumarins from Cedrelopsis grevei (Ptaeroxylaceae).

The stem bark of Cedrelopsis grevei Baill. has yielded the first reported examples of 5-prenylated coumarins, cedrecoumarin A and B as well as the known coumarins, cedrelopsin, scoparone, O-methylcedrelopsin and norbraylin, and the known chromones ptaeroglycol and ptaeroxylinol.

High prevalence of anal squamous intraepithelial lesions and squamous-cell carcinoma in men who have sex with men as seen in a surgical practice.

Introduction: Anal high-grade squamous intraepithelial lesions are probable invasive anal squamous-cell cancer precursors, and although unproved, treatment of high-grade squamous intraepithelial lesions may prevent progression to anal squamous-cell cancer. Men who have sex with men are often treated for benign anorectal disorders without consideration given to the possibility of concurrent high-grade squamous intraepithelial lesions or anal squamous-cell cancer. We determined the prevalence of anal high-grade squamous intraepithelial lesions and anal squamous-cell cancer in an urban surgical practice of men who have sex with men referred for treatment of anal condyloma and other benign noncondylomatous anal disorders.