Publications

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC₅₀ values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds <b>5j</b> and <b>6k</b> had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (<b>1</b>). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

Reading more than 100 fields per smear or examining a third sputum has insufficient marginal returns to justify the workload. Examining morning samples only is more efficient, and their collection does not necessarily inconvenience patients. Treatment can be started on the basis of one positive smear. Provided that a well functioning system of smear-microscopy quality control is in place, we propose a strategy based on examination of two morning sputum samples for negative suspects, with the diagnosis based on a single positive result.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A broad variety of herpes simplex virus type 1 clones was selected under a single round of high-dose selection with brivudin. Mutations in the thymidine kinase (TK) genes consisted of 42% frameshift mutations within homopolymer repeats of G's and C's and single nucleotide substitutions (58%) that produced stop codons (Q261 and R281) or a new codon at the site of the substitution (A168T, R51W, G59W, G206R, R220H, Y239S, and T287 M). The A168T change, associated with an altered TK phenotype, proved to be the most commonly selected substitution. For the different mutants, a correlation between phenotype, genotype, and in vivo neurovirulence was observed.

International audience

Dypiridamole (DPM) is widely used in the treatment of cardiovascular diseases as a coronary vasodilator and inhibitor of platelet aggregation. Phosphonylmethoxyethyl (PME) and 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) derivatives of purines and pyrimidines are potent and selective inhibitors of varicella-zoster virus (VZV), herpes simplex virus (HSV) and human cytomegalovirus (HCMV). We have found that DPM markedly potentiates the antiviral effects of the PME derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP), and of the HPMP derivatives of adenine (HPMPA), 3-deazaadenine (HPMPc 3 A) and cyclic HPMPA (cHPMPA). This was reflected by a significant decrease in the 50% inhibitory concentration of the acyclic nucleoside phosphonates for VZV-, HSV- and HCMV-induced cytopathic effect or plaque formation. DPM did not enhance the activity of vidarabine, acyclovir or ganciclovir. These results were confirmed by virus yield assays (for HSV and HCMV) and flow cytometry (for VZV).