L-Aspartic acid pyridinium salts: In silico, synthesis and adjuvant vs antibiotic antibacterial evaluation

• Published in: Results in Chemistry 2024-01, Vol.7, p.101366, Article 101366
• Main Authors: Gutiérrez Cano, Jessica R., Paulina Morales-Sandoval, I., Gnecco, Dino, Carrasco-Carballo, Alan, Terán, Joel L.
• Format: Article
• Language: English
• Subjects: Adjuvant; Antibiotic; L-Aspartic acid; Molecular docking; Pyridinium salts
• ISSN: 2211-7156; 2211-7156
• DOI: 10.1016/j.rechem.2024.101366

[Display omitted] •L-Aspartic pyr salts can cross membranes and affect CATIII, DNA GyrB and TryRS.•L-Aspartic pyr salts are effective as antibiotics with MIC comparable to ref. ATB.•L-Aspartic pyr salts are effective as adjuvants against chloramphenicol-resistant E. coli.•3o and 3k are comp. with ATB plus adjuvant against E. coli resistant to chloramphenicol.•Relationship between TryRS, DNA GyrB and CATIII in in silico studies with ATB. In the present study, a new series of chiral L-aspartic acid pyridinium salts have been designed, guided by molecular docking as antiemetics via TrySR or DNA GryB inhibitors, as well as an adjuvant to chloramphenicol via CAT-III inhibitor to continue with antibacterial in vitro study. Newly designed molecules have been synthesized by chemistry route and their characterization was done by using NMR & HRMS techniques. Biological evaluation of synthesized compounds has been done on Gram-negative bacteria, to E. coli The in vitro evaluation results have shown that pyridinium salts 3a, 3e, 3i, 3j, 3k and 3o as an antibacterial, in addition to 3o and 3i, as an adjuvant against E. coli resistant to chloramphenicol.