Search

Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC50 values for 3-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.

Deals with a study which examined the corrosion performance of commercially pure titanium and three alloys in two tribo-corrosion situations. Background on the corrosion resistance of titanium; Discussion on several experimental techniques such liquid-solid impingement and cavitation-corrosion tests; Information on the effect of erosion and cavitation on corrosion.

The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of l-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 μM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of l-chicoric acid (l-CA) showed improved selectivity over l-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.

The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure−activity relationships were employed to synthesize compounds with:  (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0.07 to >10 μM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 μM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were d-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-l-tartaric acid, digalloyl-l-tartaric acid, bis(3,4-dihydroxybenzoyl)-l-tartaric acid, dicaffeoylglyceric acid, and bis(3,4-dihydroxyphenylacetyl)-l-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 μM. Structure−activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.

Examines the battle for the heart and mind of the Canadian automobile buyer. Nissan in the lead; So far, mostly a war of words at General Motors Canada and Ford Canada; The emphasis placed by Nissan on customer satisfaction; The need to hire salespeople with integrity; The need to take a longer view to develop customer loyalty. INSET: Car dealers' class act..

Comments on Toyota's car plant in Cambridge, Ontario. Employees chosen for their teamwork skills, not their assembly line experience; Attitude, flexibility and knack for spotting flaws; Cooperation between managers and line workers; The Japanese philosophy of `kaizen,' or continuous improvement. INSET: Bob White: It's an attack on worker solidarity (stand of....

Reports on vehicles used by corporate treasurers and chief financial officers to maximize their capital. Use of hedges, options and swaps; Protection against foreign exchange and interest rate risks; Dangers involved; Attitudes of senior management.

Profiles Eike Batista, 34, chairman of TVX Gold Inc., recently formed by merging Inco Ltd.'s Inco Gold Inc. and Consolidated TVX Mining Corp. Batista began his career over a decade ago by trading goods in his native Brazil.

Details how research and development paid off for Canstar Sports Inc., a Montreal-based company that manufactures hockey equipment. How many skates they sell; Description of the company; Why it is unique in its commitment to industrial design and its skill at managing the efforts of its designers; How the skates are developed.

Thirty-one isolates of the form genera Acremonium and Cephalosoporium were screened for their ability to excrete enzymes capable of degrading β-glucans. Most produced both (1 → 3)- and (1 → 6)-β-glucanases together, although the yields varied with carbon source used. Surprisingly, higher yields of (1 → 3)-β-glucanases were often seen from isolates grown on pustulan, a (1 → 6)-β-glucan which is not hydrolysed by these enzymes. Lower enzyme yields were generally obtained with glucose than with either laminarin, a (1 → 3)-β-glucan or pustulan as carbon sources, suggesting regulation of synthesis by either catabolite repression and/or induction. However, a few isolates, most notably Cephalosporium sp. OXF C13 and Acremonium strictum appeared to have some constitutive-β-glucanase activity. Most of the isolates screened were only very weakly cellulolytic against carboxymethyl cellulose or filter paper as substrates.