Identification of Some Glutamic Acid Derivatives with Biological Potential by Computational Methods

Glutamic acid is a non-essential amino acid involved in multiple metabolic pathways. Of high importance is its relationship with glutamine, an essential fuel for cancer cell development. Compounds that can modify glutamine or glutamic acid behaviour in cancer cells have resulted in attractive anticancer therapeutic alternatives. Based on this idea, we theoretically formulated 123 glutamic acid derivatives using Biovia Draw. Suitable candidates for our research were selected among them. For this, online platforms and programs were used to describe specific properties and their behaviour in the human organism. Nine compounds proved to have suitable or easy to optimise properties. The selected compounds showed cytotoxicity against breast adenocarcinoma, lung cancer cell lines, colon carcinoma, and T cells from acute leukaemia. Compound 2Ba5 exhibited the lowest toxicity, and derivative 4Db6 exhibited the most intense bioactivity. Molecular docking studies were also performed. The binding site of the 4Db6 compound in the glutamine synthetase structure was determined, with the D subunit and cluster 1 being the most promising. In conclusion, glutamic acid is an amino acid that can be manipulated very easily. Therefore, molecules derived from its structure have great potential to become innovative drugs, and further research on these will be conducted.