Synthesis and biological evaluation of 3,4-dihydro-1H-[1,4] oxazepino [6,5,4-hi] indol-1-ones and 4,6-dihydrooxepino [5,4,3-cd] indol-1(3H)-ones as Mycobacterium tuberculosis inhibitors

Bastien Champciaux; Clément Raynaud; Albertus Viljoen; Loïc Chene; Jérôme Thibonnet; Stéphane P Vincent; Laurent Kremer; Emilie Thiery

doi:10.1016/j.bmc.2021.116248

Synthesis and biological evaluation of 3,4-dihydro-1H-[1,4] oxazepino [6,5,4-hi] indol-1-ones and 4,6-dihydrooxepino [5,4,3-cd] indol-1(3H)-ones as Mycobacterium tuberculosis inhibitors

Bioorg Med Chem. 2021 Aug 1:43:116248. doi: 10.1016/j.bmc.2021.116248. Epub 2021 Jun 7.

Authors

Bastien Champciaux¹, Clément Raynaud², Albertus Viljoen², Loïc Chene³, Jérôme Thibonnet¹, Stéphane P Vincent³, Laurent Kremer⁴, Emilie Thiery⁵

Affiliations

¹ Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France.
² Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS UMR 9004, Université de Montpellier, 34293 Montpellier, France.
³ Department of Chemistry, University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium.
⁴ Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS UMR 9004, Université de Montpellier, 34293 Montpellier, France; INSERM, IRIM, 34293 Montpellier, France.
⁵ Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France. Electronic address: emilie.thiery@univ-tours.fr.

PMID: 34274760
DOI: 10.1016/j.bmc.2021.116248

Abstract

This study focuses on the synthesis of 1,7- and 3,4-indole-fused lactones via a simple and efficient reaction sequence. The functionalization of these "oxazepino-indole" and "oxepino-indole" tricycles is carried out by palladium catalysed CC coupling, nucleophilic substitution or 1,3-dipolar cycloaddition. The evaluation of their activity against Mycobacterium tuberculosis shows that the "oxazepino-indole" structure is a new inhibitor of M. tuberculosis growth in vitro.

Keywords: Heterocycles; Indoles; Inhibitor; Mycobacterium tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Dose-Response Relationship, Drug
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents