Préparation de nouveaux matériaux à base de (benz)imidazole et bio-activité

Abstract

The first part, which is subdivided into two chapters, concerns the synthesis, characterization (IR and UV-Vis, X-ray diffraction, and other elemental analysis) and biological evaluation of divalent transition metal complexes (M = Co , Cu, Cd, Zn, Ni) based on (1-methyl-1Hbenzo[d]imidazol-2-yl) methanol (L1/Hmbm) (complexes 1-4) and (1-methyl-1H- imidazol-2-yl) methanol (L2/Hmim) (complexes 5-11). In both series of coordination compounds, the ligand (L1 or L2) gives rise to a variety of metal-ligand coordination modes(monodentate or bidentadate) exhibiting tetrahedral or octahedral geometry.The in vitro measurement of the antioxidant activity of the L1 and L2 ligands and their respective metal complexes against the free radical scavenger DPPH at low concentration (100 &g / mL), showed a moderate to significant antioxidant activities, compared to the standard (Asc). The complexes (5-11) and the ligand L2 were submitted to an in vitro evaluation of their antimicrobial activity against five pathogenic strains: animal bacteria: Gram (+) (S. aureus) and Gram (-) (K pneumonia), a Gram (+) phytopathogenic bacterium (P. syringae), a yeast (P. caribbica) and a fungus (Trichodermsp), using the disk diffusion method (agar).The analysis of the results revealed a significant difference in the inhibition profile of the selected strains. The complex 5 and to a lesser extent the complex 6, gave the best results displaying significant inhibitory activities on mostly all pathogenic strains (broad spectrum). In the second part dedicated to the synthesis of structural analogs of Tacrine, a whole series of new poly-heterocyclic compounds (10-14) was prepared from the corresponding 4H-pyrans (5- 9) by an addition-hetero-cyclization reaction of cyclohexanone under the Friedl‰ndler's standard conditions reaction. The in vitro antioxidant tests (DPPH and ABTS) of benzimidazopyranotacrines, showed that the five compounds have an antioxidant activities, and the 5-Amino-2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano [2,3-b]uinolin-3-yl) ethanone (compound 12) is the most efficient, exhibiting a comparable inhibitory power of free radicals to that of reference compounds (controls). The structure of all the complexes (1-11) was determined by X-ray diffraction, IR, UV and other elemental analysis. For complexes 1-4, theoretical studies using DFT and TD-DFT calculations have been performed and confirmed the experimental results. Benzimidazopyranotacrines (10-14) as structural Tacrine's analogues and their intermediates 4Hpyrans (5-9), were identified by the usual spectroscopic methods (IR, 1H NMR and13C).