Synthèse et évaluation in vitro de l’activité antibactérienne d’analogues de Cadiolide.

Abstract

The emergence of bacteria that have become resistant to antibiotics has forced many research groups to discover new antibacterial compounds. Among them, cadiolides, a class of marine natural products, isolated for the first time from Botryllus sp., have been shown to be effective in inhibiting the growth of MRSA at similar or lower concentrations than current major antibiotics. Thus, the aim of this work is to expand the existing cadiolide analogue range and evaluate their antibacterial power. The first part of this thesis is divided in two folds: the first is devoted to the synthesis of cadiolide analogue by variation of the groups adjacent to the central nucleus; the synthesis was carried out by using a multi-component reaction by microwave irradiation, with a variety of keto-alcohols, aromatic aldehydes and functionalized dioxinones in the presence of a base. The second fold concerns the change in the nature of the central cycle of the cadiolide by replacing oxygen with sulphur or nitrogen. The second part consists in the study of the evaluation of the antibacterial activity of prepared cadiolide analogues, on the in-vitro growth of the different bacterial strains resistant and to study the influence of different groups carried by the central nucleus of analogues. In addition, a cytotoxicity test for the active compounds was carried out against keratinocyte cells in culture.