New Antibacterial Cadiolide Analogues active Against Antibiotic Bacterial Resistant Strains

S Bekri (1) , Florie Desriac (2) , Magalie Barreau (2) , Thomas Clamens (2) , Thibault Gallavardin (3) , Patricia Le Nahenec-Martel (3) , Julien Vieillard (3) , Yazid Datoussaid (1) , Noureddine Choukchou-Braham (1) , Olivier Lesouhaitier (2) , Xavier Franck (3) , Stéphane Leleu (3)

1 Laboratoire de Catalyse et Synthèse en Chimie Organique
2 LMSM - Laboratoire de Microbiologie Signaux et Microenvironnement
3 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

The synthesis of new cadiolide analogues was carried out using a one-pot multi component synthesis. The antibacterial activity of these molecules was evaluated on standard and antibiotic resistant bacterial strains chosen for their involvement in human health or in food-born poisoning. Four molecules have shown good activities with MICs of 2 μg/mL−1. The introduction of an indole group or the conversion of the lactone into lactam have highlighted two new families of molecules with promising antibacterial activity. In addition, most of these active molecules are devoid of cytotoxic activity against keratinocyte cells.

Keywords: Cadiolide analogues; Antibacterial; Antibiotic-resistance; Natural products

Domains: Chemical Sciences; Medicinal Chemistry

S Bekri, Florie Desriac, Magalie Barreau, Thomas Clamens, Thibault Gallavardin, et al.. New Antibacterial Cadiolide Analogues active Against Antibiotic Bacterial Resistant Strains. Bioorganic and Medicinal Chemistry Letters, 2020, 30 (21), pp.127580. ⟨10.1016/j.bmcl.2020.127580⟩. ⟨hal-02955268⟩