Niclosamide Is Active In Vitro against Mycetoma Pathogens

Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamide in particular, as drug repurposing candidates for mycetoma.     

Spacer length dependence of TGBC* and SmA phases in cholesteryl and dihydrocholesteryl-containing trimer liquid crystals

Two series of trimer liquid crystals were investigated that contain a biphenylyl central group and two cholesteryl or dihydrocholesteryl terminal mesogenic groups. Only compounds with even spacers were investigated. The dihydrocholesteryl-containing trimers show a triply intercalated smectic A (SmA) phase when the spacer lengths are greater than 8, whereas the cholesteryl-containing trimers exhibit this triply intercalated SmA phase when the spacer lengths are more than 6. With shorter spacers, a twist grain boundary C* (TGBC*) phase was found. This is revealed by the formation of a typical dotted square grid pattern upon cooling from the chiral nematic (N*) phase in the planar texture. The dots are spaced by a distance of about 1.5-1.8 µm. Upon cooling from the N* phase in the focal conic texture a striped pattern is observed with the same spacing. X-ray diffraction revealed a repeat distance for the TGBC* phase that corresponds with a monolayer ordering. The results show that the weaker interaction between the dihydrocholesteryl groups compared with cholesteryl groups or longer spacers destabilize the monolayer TGBC* phase.     

Sur les fonctions conjuguées

Sans résumé     

A New Upper Bound for the Dimension of Trace Codes

We shall derive a new non-trivial upper bound for the dimensionof trace codes connected to algebraic-geometric codes. Furthermore,we shall deduce their true dimension if certain conditions aresatisfied.     

Cover-preserving order embeddings into Boolean lattices

It is not known which finite graphs occur as induced subgraphs of a hypercube. This is relevant in the theory of parallel computing. The ordered version of the problem is: Which finite posets P occur as cover-preserving subposets of a Boolean lattice? Our main Theorem gives (for 0,1-posets) a necessary and sufficient condition, which involves the chromatic number of a graph associated to P. It is applied respectively to upper balanced, meet extremal, meet semidistributive, and semidistributive lattices P. More specifically, we consider isometric embeddings of posets into Boolean lattices. In particular, answering a question of Ivan Rival to the positive, a nontrivial invariant for the covering graph of a poset is found.     

Permutation groups generated by cycles of fixed length

Combinatorial conditions on a set of cycles of fixed degree inS _n are studied, so that they generateA _n orS _n . It is shown thatA _n orS _n is so generated if and only if a graph associated with the set of cycles is connected, provided two of the cycles satisfy certain, not too restrictive, criteria. As a corollary, the minimum number of cycles of degreem ≧ 2 that generateA _n or S_n is determined.