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Synthesis of Long‐Chain β‐Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria
Author(s) -
Santucci Pierre,
Dedaki Christina,
Athanasoulis Alexandros,
Gallorini Laura,
Munoz Anaïs,
Canaan Stéphane,
Cavalier JeanFrançois,
Magrioti Victoria
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800720
Subject(s) - resazurin , mycobacterium marinum , isoniazid , mycobacterium tuberculosis , antimycobacterial , antibiotics , antibacterial activity , microbiology and biotechnology , mycobacterium , chemistry , lactone , tuberculosis , antibacterial agent , pathogenic bacteria , bacteria , stereochemistry , biology , medicine , genetics , pathology
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.