Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics

In this study, we report the semisynthesis and in vitro biological evaluation of thirty-four derivatives of the fungal depsidone antibiotic, unguinol. Initially, the semisynthetic modifications were focused on the two free hydroxy groups (3-OH and 8-OH), the three free aromatic positions (C-2, C-4 and C-7), the butenyl side chain and the depsidone ester linkage. Fifteen first-generation unguinol analogues were synthesised and screened against a panel of bacteria, fungi and mammalian cells to formulate a basic structure activity relationship (SAR) for the unguinol pharmacophore. Based on the SAR studies, we synthesised a further nineteen second-generation analogues, specifically aimed at improving the antibacterial potency of the pharmacophore. In vitro antibacterial activity testing of these compounds revealed that 3-O-(2-fluorobenzyl)unguinol and 3-O-(2,4-difluorobenzyl)unguinol showed potent activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MIC 0.25–1 μg mL⁻¹) and are promising candidates for further development in vivo.Mahmud T. Morshed, Hang T. Nguyen, Daniel Vuong, Andrew Crombie, Ernest Lacey, Abiodun D. Ogunniyi, Stephen W. Page, Darren J. Trott and Andrew M. Piggot

Geometry optimization of uncoated silicon microcantilever-based gas density sensors

International audienceIn the absence of coating, the only way to improve the sensitivity of silicon microcantilever-based density sensors is to optimize the device geometry. Based on this idea, several microcantilevers with different shapes (rectangular-, U-and T-shaped microstructures) and dimensions have been fabricated and tested in the presence of hydrogen/ nitrogen mixtures (H 2 /N 2) of various concentrations ranging from 0.2% to 2%. In fact, it is demonstrated that wide and short rectangular cantilevers are more sensitive to gas density changes than U-and T-shaped devices of the same overall dimensions, and that the thickness doesn't affect the sensitivity despite the fact that it affects the resonant frequency. Moreover, because of the phase linearization method used for the natural frequency estimation, detection of a gas mass density change of 2 mg/l has been achieved with all three microstructures. In addition, noise measurements have been used to estimate a limit of detection of 0.11 mg/l for the gas mass density variation (corresponding to a concentration of 100 ppm of H 2 in N 2), which is much smaller than the current state of the art for uncoated mechanical resonators