Potential medical applicability of N-β-Ala and N-His dipeptidomimetics against breast cancer: short in vitro and in silico screening

Short peptides conjugated to drugs are found to effectively improve wellbeing and recovery of cancer patients. However, to combat poor stability and bioavailability, their polar groups can be protected to form mimetics. Therefore, here we present synthesis, short biological screening and detailed computational analysis of 18 N-terminal β-alanine and L-histidine dipeptidomimetics, to estimate their preliminary relevance as cancer therapeutics intermediates for conjugation. While extended biological experiments are deeply relevant to define drug functionality, they also require extensive financial resources. Herein, we employed computational methods to better estimate possible activities of the compounds, and create a perspective between in silico and in vitro to hypothesize on the acquired results. Most efficient representatives of each group were β-Ala-Ala (BAA) and His(Bn)-Val (HV) dipeptidomimetics, which seem to show signs of selectivity. Our research provides detailed theoretical data for scientists searching for their new conjugative agents to study. We hope to encourage other experts to incorporate computational methods into their research, to increase clarity and available data for further research.