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
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.