Simon Feldbaek Nielsen

Antileishmanial chalcones : Statistical design, synthesis, and three-dimensional quantitative structure-activity relationship analysis

A large number of substituted chalcones have been synthesized and tested for antileishmanial and lymphocyte-suppressing activities. A subset of the chalcones was designed by using statistical methods. 3D-QSAR analyses using 67 (antileishmanial activity) and 63 (lymphocyte-suppressing activity) of the compounds for the training sets and 9 compounds as an external validation set were performed by using the GRID/GOLPE methodology. The Smart Region Definition procedure with subsequent region selection as implemented in GOLPE reduced the number of variables to approximately 1300 yielding 3D-QSAR models of high quality (lymphocyte-suppressing model, R2 = 0. 90, Q2 = 0.80; antileishmanial model, R2 = 0.73, Q2 = 0.63). The coefficient plots indicate that steric interactions between the chalcones and the target are of major importance for the potencies of the compounds. A comparison of the coefficient plots for the antileishmanial effect and the lymphocyte-suppressing activity discloses significant differences which should make it possible to design chalcones having a high antileishmanial activity without suppressing the proliferation of lymphocytes.

The Suzuki Reaction Under Solvent-Free Conditions

Abstract The coupling reaction of diverse arylhalogenids with phenyl-boronic acid under solvent-free conditions has been performed using a palladium catalyst. The order of reactivity was complementary to the normal Suzuki reaction.

Modifications of the α,β-Double bond in chalcones only Marginally affect the antiprotozoal activities

Abstract Methods for selective alkylation of chalcones in the α- or β-position and for selective reduction of the α,β-double bond have been developed. The antiparasitic potencies of the α,β-double bond modified chalcones only differ marginally from the potencies of the parent chalcones indicating that the propenone residue only functions as a spacer between the two benzene rings, which are the true pharmacophore.

Antileishmanial Chalcones: Statistical Design and 3D-QSAR Analysis

Leishmaniasis is an often lethal disease caused by various species of the protozoan parasite Leishmania. We have shown that chalcones e.g. Licochalcone A cure leishmania infections in mice. Unfortunately the chalcones are slightly toxic as shown by the inhibition of lymphocyte proliferation. This work describes the statistical design of substituted chalcones and calculation of 3D-QSAR models for the antiparasitic and toxic effects of the chalcones.