Resumen

ORTIZ LOPEZ, Claudia. Design, synthesis, characterization and in vitro evaluation of antimicrobial peptides against pathogenic bacteria resistant to antibiotics. Rev. acad. colomb. cienc. exact. fis. nat. [online]. 2019, vol.43, n.169, pp.614-627. ISSN 0370-3908.  https://doi.org/10.18257/raccefyn.864.

Antimicrobial peptides have attracted much attention as new therapeutic agents against infectious diseases. In this work, we made the rational in silico design of 18 cationic peptides with antimicrobial activity against resistant pathogenic bacteria using the DEPRAMP software developed in the GIBIM research group. Subsequently, the designed peptides were synthesized in solid phase using the Fmoc strategy in an acid medium. Then, sequences of 17 amino acids were obtained with a degree of purity between 95 and 98%, secondary structure α-helix, net cationic charge (between +3 and +6), pI between 10.04 to 12.03, and hydropathy index between -0.62 and 1.14. All antimicrobial peptides showed antibacterial and bactericidal activity in vitro against at least one of the pathogenic strains studied: Escherichia coli O157: H7, Pseudomonas aeruginosa, and Staphylococcus aureus Resistant to Methicillin. The GIBIM-P5S9K and GIBIM-P5F8W antimicrobial peptides presented the best antibacterial activities reaching MIC99 in ranges of 0.5 to 25 μM against the three strains evaluated. E. coli O157: H7 was the most sensitive strain to the GIBIMP5F8W presenting 0.5 μM MIC99 and 10 μM MBC, and P. aeruginosa was the most resistant strain with MIC values over 100 μM against more than five antimicrobial peptides. The toxicity of peptides in erythrocytes produced a hemolysis percentage of less than 40% in concentrations of 50 μM. On the other hand, in the lung carcinoma cell lines A549 and HepG2, the only compound that presented toxicity was GIBIM-P5F8W, presenting 36% of viable cells in concentrations of 100 μM of the peptide in the A549 cell line.

Palabras clave : Antimicrobial peptides; microbial resistance; antimicrobial activity.

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