|
|||||
|
|
Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria |
|
| Authors: | Pierre Santucci Christina Dedaki Alexandros Athanasoulis Laura Gallorini Anaïs Munoz Dr Stéphane Canaan Dr Jean-François Cavalier Dr Victoria Magrioti |
| Affiliation: | 1. Aix-Marseille Université, CNRS, LISM, IMM FR3479, Marseille, France
These authors have contributed equally to this work.;2. Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, 15771 Greece These authors have contributed equally to this work.;3. Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, 15771 Greece;4. Aix-Marseille Université, CNRS, LISM, IMM FR3479, Marseille, France |
| Abstract: | In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents. |
| Keywords: | antibacterial activity Mycobacterium marinum serine hydrolases tuberculosis β-lactones |