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Article

Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents

1
School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
2
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
3
School of Life Sciences, University of Technology Sydney, P.O. Box 123, Ultimo, NSW 2007, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Axel T. Neffe
Int. J. Mol. Sci. 2022, 23(9), 4623; https://doi.org/10.3390/ijms23094623
Received: 31 December 2021 / Revised: 16 April 2022 / Accepted: 16 April 2022 / Published: 21 April 2022
(This article belongs to the Special Issue New Molecular Designs for Drugs including Potential Antibiotics)
There is a significant and urgent need for the development of novel antibacterial agents to tackle the increasing incidence of antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics are reported as potential new leads to treat bacterial infection. Here, we describe the design, synthesis and biological evaluation of cholic acid-based small molecular antimicrobial peptide mimics. The synthesis of cholic acid analogues involves the attachment of a hydrophobic moiety at the carboxyl terminal of the cholic acid scaffold, followed by the installation of one to three amino acid residues on the hydroxyl groups present on the cholic acid scaffold. Structure–activity relationship studies suggest that the tryptophan moiety is important for high antibacterial activity. Moreover, a minimum of +2 charge is also important for antimicrobial activity. In particular, analogues containing lysine-like residues showed the highest antibacterial potency against Gram-positive S. aureus. All di-substituted analogues possess high antimicrobial activity against both Gram-positive S. aureus as well as Gram-negative E. coli and P. aeruginosa. Analogues 17c and 17d with a combination of these features were found to be the most potent in this study. These compounds were able to depolarise the bacterial membrane, suggesting that they are potential antimicrobial pore forming agents. View Full-Text
Keywords: cholic acid; antimicrobial peptide; peptidomimetics; antibacterial; membrane disruption cholic acid; antimicrobial peptide; peptidomimetics; antibacterial; membrane disruption
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MDPI and ACS Style

Wu, J.; Yu, T.T.; Kuppusamy, R.; Hassan, M.M.; Alghalayini, A.; Cranfield, C.G.; Willcox, M.D.P.; Black, D.S.; Kumar, N. Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents. Int. J. Mol. Sci. 2022, 23, 4623. https://doi.org/10.3390/ijms23094623

AMA Style

Wu J, Yu TT, Kuppusamy R, Hassan MM, Alghalayini A, Cranfield CG, Willcox MDP, Black DS, Kumar N. Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents. International Journal of Molecular Sciences. 2022; 23(9):4623. https://doi.org/10.3390/ijms23094623

Chicago/Turabian Style

Wu, Jie, Tsz Tin Yu, Rajesh Kuppusamy, Md. Musfizur Hassan, Amani Alghalayini, Charles G. Cranfield, Mark D. P. Willcox, David StC. Black, and Naresh Kumar. 2022. "Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents" International Journal of Molecular Sciences 23, no. 9: 4623. https://doi.org/10.3390/ijms23094623

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