Evaluation of new antimicrobial agents on Bacillus spp. strains: docking affinity and in vitro inhibition of glutamate-racemase

Abstract

Three glutamic acid derivatives, two boron-containing and one imide-containing compound, were synthesized and tested for antimicrobial activity targeting glutamate-racemase. Antimicrobial effect was evaluated over Bacillus spp. Docking analysis shown that the test compounds bind near the active site of racemase isoforms, suggesting an allosteric effect. The boron derivatives had greater affinity than the imide derivative. In vitro assays shown good antimicrobial activity for the boron-containing compounds, and no effectiveness for the imide-containing compounds. The minimum inhibitory concentration of tetracycline, used as standard, was lower than that of the boron-containing derivatives. However, it seems that the boron-containing derivatives are more selective for bacteria. Experimental evidence suggests that the boron-containing derivatives act by inhibiting the racemase enzyme. Therefore, these test compounds probably impede the formation of the bacterial cell wall. Thus, the boron-containing glutamic acid derivatives should certainly be of interest for future studies as antimicrobial agents for Bacillus spp.

Keywords::

• Docking
• glutamic acid
• racemase enzyme inhibitors
• boron-containing compounds

Acknowledgments

The authors are grateful to CONACyT (132353), ICyTDF (PIRIVE 09-9), SIP, COFAA/IPN EDI/IPN and the scholarship from CONACyT to Feliciano Tamay-Cach. We thank Bruce Allan Larsen for reviewing the use of English in the manuscript.

Conflict of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the article.