Abstract
Antimicrobial peptides are thought to be promising antibiotic substitutes for a variety of multidrug-resistant bacteria. Nevertheless, there are several issues with their clinical and commercial development, such as the high cost of peptide manufacturing and the susceptibility to proteases. Peptide mimics include peptoids have emerged as a promising substitute for antimicrobial peptides, since they are resistant to enzymatic degradation and exhibit significant antibacterial action. In this study we have examined the potential of a newly designed peptoid PPT, which is based on an amphipathic template of the cationic peptide A-12. Using the microbroth dilution method, antimicrobial activity of synthesized compounds was tested on various bacterial strains including a gentamicin- resistant E. coli. Human RBCs and HEK 293 cells were employed for a cytotoxicity study, and SEM was used to see the morphological changes induced by peptidomimetics on E. coli. Further, the checkerboard method aimed to investigate synergy between peptide –antibiotics combination against various bacterial and fungal strains. Results suggested that PPT exhibit significant antimicrobial activity even in the presence of different salts with MICs ranges from 64 to 3.1 µg/ml against tested strains. Based on FIC values, PPT showed additive effect in combination with gentamicin against E. coli and synergistic effect in combination with fluconazole, amphotericin B and tetracycline against A. niger, A. flavus and E. coli. Additionally, PPT showed low toxicity to hRBCs and kidney cell lines. Furthermore, the microscopic examination has shown that peptoid has the potential to damage the cell membranes of E. coli. Overall, the easier synthesis and potent antimicrobial activity makes PPT a suitable candidate for drug development.
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Acknowledgements
We would like to acknowledge JUIT, Solan for providing research facilities. We would also thank to Dr. Jata Shankar, Biotechnology department JUIT and ASBASJS Memorial College of Pharmacy, Punjab for their support in our study of fungal strains and drug resistant strain respectively.
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This study was supported by the Indian Council of Medical Research (ICMR), Delhi, (Grant Number; 52/4/2013- Bio BMS).
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All authors contributed to the study conceptions and designs. Material preparations, data collection, and manuscript were written by LS. Dr. GSB read, analyze and approved the final manuscript for publication.
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Sharma, L., Bisht, G.S. In Vitro Biological Evaluation and Mechanism of Action of Peptoid Analogue Based on Cationic, Amphipathic Peptide A-12. Int J Pept Res Ther 29, 98 (2023). https://doi.org/10.1007/s10989-023-10566-7
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DOI: https://doi.org/10.1007/s10989-023-10566-7