Synthesis and antimicrobial activity of some benzoxazinoids derivatives of 2-nitrophenol and 3-hydroxy-2-nitropyridine

Abstract

Benzoxazinoids (BXs), alkaloids frequently found in Gramineae species, are natural defensives that can potentially be exploited to the development of novel antimicrobial agents. Here, BXs analogs were synthesized from 2-nitrophenol (benzoxazinone series) and 3-hydroxy-2-nitropyridine (pyridoxazinone series) and tested against fungal and bacteria of medical interest. The starting materials were submitted to adequate nucleophilic substitution in order to functionalize of analogs, followed by a reductive cyclization catalyzed by palladium on carbon. Next, the biological assays showed that pyridoxazinone serie has a good antibacterial activity, especially against Enterococcus faecalis (Minimum inhibitory concentration—MIC: 7.8-15.6 μg.mL⁻¹) and Acinetobacter baumannii (MIC 31.25-125 μg.mL⁻¹). Antifungal activity, in turn, was related to compound 2e which showed a MIC of 62.5 μg.mL⁻¹ against Candida albicans, Candida glabrata, and Candida tropicalis. All analogs complied with Lipinski's rules and were predicted to have a low toxicity.

Graphical Abstract

Keywords:

• Benzoxazinones
• pyridoxazinones
• antifungal activity
• antibacterial activity
• cytotoxicity
• chemo-informatics

Acknowledgments

W.G.L. is grateful to Fundação de Amparo à Pesquisa de Minas Gerais (FAPMIG) for a graduate fellowship. JMS acknowledge Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for a research grant.

Disclosure statement

The authors declare that they have no conflict of interest. All authors contributed to the development, analysis, and drafting of this article.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal do Nível Superior (CAPES) under Grant 2833-2011.