Hubert Duran

Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents

Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.

Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties.

Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but only moderate antioxidant activity, so that high concentrations are required for inhibiting LDL oxidation. We aimed to develop agents sharing both antioxidant and carbonyl scavenger properties. We have synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH). BVH strongly inhibited LDL oxidation induced by copper and by human endothelial cells (HMEC-1), and prevented the formation of macrophagic foam cells. BVH reduced both the extracellular generation of ROS (superoxide anion and hydrogen peroxide) induced by oxidized LDL (oxLDL), as well as intracellular oxidative stress and proteasome activation, NFkappaB activation, and oxLDL-mediated proinflammatory signaling. In parallel, BVH prevented the carbonyl stress induced by oxLDL on cellular proteins, and blocked the apoptotic cascade as assessed by the inhibition of Bid cleavage, cytochrome C release, and DEVDase activation. Lastly, BVH prevented atherogenesis and carbonyl stress in apoE(-/-) mice. In conclusion, BVH is the prototype of a new class of antioxidant and carbonyl scavenger agents designed for new therapeutical approaches in atherosclerosis.

N-(2-pyridyl)-3-phenyl-2-propene amide (O-N) complexes fo copper(II), nickel(II), cobalt(II) and palladium(II). Crystal and molecular structure of Cu(O-N)2(CF3SO3)2

Abstract The reaction of the title ligand N-(2-pyridyl)-3-phenyl-2-propene amide (O-N) with MX2 salts yields compounds of the type M(O-N)2X2 and [M(O-N)2(H2O)2]X2, which were characterized by elemental analysis, magnetic moments and IR and EPR spectroscopies. From the IR spectra the ligand is found to be bidentate via the pyridyl nitrogen and the amide oxygen, except in [Pd(O-N)2Cl2] where only the pyridyl ring is coordinated. The magnetic moments, IR spectra and thermograms of the M(O-N)2(NO3)2·3H2O compounds [M = nickel(II), cobalt(II)] are consistent with the presence of trans-[M(O-N)2(H2O)2]2+ ions, similar to the trans-[Zn(O-N)2(CH3OH)2]2+ species observed earlier. The EPR spectra of the trans-Cu(O-N)2X2 compounds (X = NO3−, CF3SO3−) indicate an elongated octahedral coordination with equatorial bidentate (O-N) ligands and solvent molecules or anions in axial sites. The solid-state spectra reveal the presence of more than one type of copper(II) centre. The crystal structure of trans-Cu(O-N)2(CF3SO3)2 was determined by X-ray diffraction. The unit cell contains two types of discrete trans-Cu(O-N)2(CF3SO3)2 molecules, in which bidentate (O-N) ligands are strongly bonded to the equatorial sites of a tetragonally distorted octahedron. The axial positions are filled by

New recurrent synthetic method for the synthesis of functionalized oligomeric β-O-4 lignin model compounds

Abstract β-O-4 lignin model compounds have been synthesized using a new recurrent method affording dimers and trimers with controlled stereochemistry and bearing an aldehyde group.

Synthesis of phosphonocinnamic thioesters, substrate analogues of cinnamoyl-CoA reductase, a key enzyme in the lignification process

Abstract The one-pot transesterification of diethylarylvinylphosphonates with N -acetylcysteamine has been achieved using phosphonochloridates as intermediates. Reaction of phosphonodiesters with (COCl) 2 gave the corresponding chlorinated compounds, which were coupled with N -acetylcysteamine in presence of Et 3 N.