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

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 mu g.mL(-1)) and Acinetobacter baumannii (MIC 31.25-125 mu g.mL(-1)). Antifungal activity, in turn, was related to compound 2e which showed a MIC of 62.5 mu g.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. [GRAPHICS]