D-amino Acids: Prospects for New Therapeutic Agents

D-amino acids are predominantly produced and utilized by bacteria. They are involved in the synthesis and cross-linking of peptidoglycan. Furthermore, oxidative catabolism of D-amino acids, via the D-amino acid dehydrogensae pathway, sustains energy production for cellular functions. Only a few decades ago, it was largely believed that free D-amino acids were restricted to bacteria. Often, D-amino acids were considered as the by-products of bacterial metabolism. Nevertheless, the occurrence of Damino acids in mammals was recently confirmed by means of sensitive and advanced analytical methods. The physiological functions of D-amino acids in humans are still under investigation. The presence of astonishing amounts of certain D-amino acids in the human Central Nervous System suggests a vital role of D-amino acids in neuromodulation. Apparently, both prokaryotes and eukaryotes maintain tight regulation on the occurrence of D-amino acids in their systems through specific metabolic pathways. Previously, it had been reported that the accumulation of certain D-amino acids results in cellular toxicity. In this study, we investigate the potential of Damino acids as prospective new therapeutic agents. Antibacterial, antifungal, and cytotoxic activities were evaluated against representative cellular models. Our findings indicate that, although D-amino acids are toxic on their own, their efficacy can be significantly improved by synergism with other therapeutic agents. The ability to use lower doses of both, the drug and D-amino acids, may be beneficial for the development of combinational remedies against resistant pathogens or cancerous cells.