Discovery and Structure-Based Optimization of 2-Ureidothiophene-3-carboxylic Acids as Dual Bacterial RNA Polymerase and Viral Reverse Transcriptase Inhibitors.

We are concerned with the development of novel anti-infectives with dual antibacterial and antiretroviral activities for MRSA/HIV-1 co-infection. To achieve this goal, we exploited for the first time the mechanistic function similarity between the bacterial RNA polymerase (RNAP) "switch region" and the viral non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Starting from our previously discovered RNAP inhibitors, we managed to develop potent RT inhibitors effective against several resistant HIV-1 strains with maintained or enhanced RNAP inhibitory properties following a structure-based design approach.

Surface plasmon resonance--more than a screening technology: insights in the binding mode of σ70:core RNAP inhibitors.

Aim: Antibiotic resistance has become a major health problem. The σ(70):core interface of bacterial RNA polymerase is a promising drug target. Recently, the coiled-coil and lid-rudder-system of the β' subunit has been identified as an inhibition hot spot.

Design and synthesis of some new theophylline derivatives with bronchodilator and antibacterial activities.

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 65 years. Recently, it was found that bacterial infection plays a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of 6-(4-(un)substituted phenyl)thiazolo[2,3-f]theophyllines 2a-g and different series of 8-(1,2,4-triazol-3-ylmethylthio)theophyllines 6-9.