New mustard-linked 2-aryl-bis-benzimidazoles with anti-proliferative activity

We describe new methodology for the synthesis of symmetric bis-benzimidazole carrying 2-aryl moieties, including 2-[4-3'-aminopropoxy)phenyl] and 2-[4-(3'-aminopropanamido)pheny] substituents, together with the synthesis of novel hybrid molecules comprising bis-benzimidazoles in ester and amide combination with the N-mustard chlorambucil. The in vitro activities of these compounds against five cancer cell lines are also provided.

Assembly intermediates in polyketide biosynthesis; enantioselective syntheses of beta-hydroxycarbonyl compounds

A versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of the acyloxazolidone intermediate using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable intermediates in the synthesis of 4-hydroxy-6-substituted gamma-lactones.

3D-QSAR studies on 4-Hydroxyphenylpyruvate Dioxygenase inhibitors by comparative molecular field analysis (CoMFA)

A comparative molecular field analysis (CoMFA) of alkanoic acid 3-oxo-cyclohex-1-enyl ester and 2-acylcyclohexane-1,3-dione derivatives of 4-hydroxyphenylpyruvate dioxygenase inhibitors has been performed to determine the factors required for the activity of these compounds. The substrate's conformation abstracted from dynamic modeling of the enzyme-substrate complex was used to build the initial structures of the inhibitors. Satisfactory results were obtained after an all-space searching procedure, performing a leave-one out (LOO) cross-validation study with cross-validation q(2) and conventional r(2) values of 0.779 and 0.989, respectively. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new HPPD ligands with predetermined affinities.

Strategies for the development of the urinary catheter.

Indwelling urinary catheters are utilized in the management of a wide range of conditions both in an acute and a chronic setting. However, utilization of this type of device is associated with a number of issues, including an increased propensity to develop bacteriuria, symptomatic infection and also encrusted deposits on the device. The development of novel biomaterials, incorporation of therapeutic agents and other strategies to minimize the issues associated with these devices are discussed in this review.