Dense resistivity and induced polarization profiling for a landfill restoration project at Härlöv, Southern Sweden.

A resistivity and time-domain induced polarization (IP) survey was conducted at a landfill site under restoration at Härlöv in Southern Sweden. The covering of the landfill had begun some years ago, without keeping precise records of the work done, as is usual in such procedures. The survey was conducted in two steps, on two adjacent areas. First, a number of geoelectrical sections were made on a partly covered area that had been investigated earlier by auger drilling, in order to assist restoration. Then, a second area that should have received its final cover was imaged, and some defects in the cover could be detected and repaired. The resistivity and time-domain IP results were consistent with the results of the geotechnical drillings, and they enabled quasi-continuous mapping along the profiles. Three-dimensional visualization showed the overall consistency of the two-dimensional lines, and helped to generate a global view of the site. In spite of some ambiguities, cover and waste could be distinguished in most cases. In particular, fine-grained cover materials could be clearly distinguished from other cover materials.

Novel selective inhibitors of the zinc plasmodial aminopeptidase PfA-M1 as potential antimalarial agents.

Proteases that are expressed during the erythocytic stage of Plasmodium falciparum are newly explored drug targets for the treatment of malaria. We report here the discovery of potent inhibitors of PfA-M1, a metallo-aminopeptidase of the parasite. These compounds are based on a malonic hydroxamic template and present a very good selectivity toward neutral aminopeptidase (APN-CD13), a related protease in mammals. Structure-activity relationships in these series are described. Further optimization of the best inhibitor yielded a nanomolar, selective inhibitor of PfA-M1. This inhibitor displays good physicochemical and pharmacokinetic properties and a promising antimalarial activity.

A library of novel hydroxamic acids targeting the metallo-protease family: design, parallel synthesis and screening.

We report here the design and parallel synthesis of 217 compounds based on a malonic-hydroxamic acid template. These compounds are obtained via a two-step solution-phase procedure. The set of diverse building-blocks used makes this strategy suitable for the search of inhibitors of various metallo-proteases and for the investigation of the biological role of new metallo-proteases. As a proof of concept, we screened this library on Neutral Aminopeptidase (APN; EC 3.4.11.2), the prototypal enzyme of the M1 family. Several submicromolar inhibitors were identified.

Design, synthesis and in vitro antimalarial activity of an acylhydrazone library.

A library of acylhydrazone iron chelators was synthesized and tested for its ability to inhibit the growth of a chloroquine-resistant strain of Plasmodium falciparum. Some of these new compounds are significantly more active than desferrioxamine DFO, the iron chelator in widespread clinical use and also than the most effective chelators.