Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy

Kurnaz, Leman Buzoglu; Luo, Yuanyuan; Yang, Xiaoming; Alabresm, Amjed; Leighton, Ryan; Kumar, Rani; Hwang, Ji Hyeon; Decho, Alan W.; Nagarkatti, Prakash; Nagarkatti, Mitzi; Tang, Chuanbing

doi:10.1016/j.bioactmat.2022.06.009

Cited by 9 publications

(9 citation statements)

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“…For S. enterica Typhimurium (ATCC 13311), the values varied from 31 to 125 μg/mL, considering 10 compounds derived from abietic acid. The work by Kurnaz et al [ 7 ] also presented the inhibition values, determined with the MIC tests, of three tricyclic compounds derived from abietic acid; for S. aureus (ATCC-29213), the concentration values were 7.8 and 31.3 μg/mL, whereas, for E. coli (ATCC-25922), they were 15.6, 250, and 125 µg/mL. In the work by Silva et al [ 17 ], the MIC value for S. aureus (ATCC 25923) was 1024 μg/mL, and that for E. coli (ATCC 25922) was 64 µg/mL, indicating that abietic acid has antimicrobial properties.…”

Section: Resultsmentioning

confidence: 99%

“…Abietic acid (C19H29COOH) is a diterpenoid that belongs to the terpene class and is found mainly in pine trees. Some works have already reported its antibacterial and antifungal efficacy; thus, abietic acid and its derivatives have an important potential as an alternative for new drugs, to be applied against antimicrobial resistance [ 5 , 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Green Synthesis of Na abietate Obtained from the Salification of Pinus elliottii Resin with Promising Antimicrobial Action

et al. 2023

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The growing concern about the emergence of increasingly antibiotic-r4esistant bacteria imposes the need to search and develop drugs to combat these microorganisms. This, combined with the search for low-cost synthesis methods, was the motivation for the elaboration of this work. Abietic acid present in the resin of Pinus elliotti var. elliotti was used to generate a sodium salt by salification. The synthesis route was low-cost, consisting of only two reaction steps at mild temperatures without toxic organic solvents, and eco-friendly and easy to conduct on an industrial scale. Sodium abietate (Na-C20H29O2) was characterized by mass spectrometry, infrared spectroscopy, elemental analysis, X-ray diffraction, scanning electron microscopy, and energy-dispersive spectroscopy. To perform the antimicrobial tests, the determination of minimum inhibitory concentration and the disk diffusion assay was performed. The results obtained showed that the salt Na abietate performed an antimicrobial action against the bacterial strains S. aureus, E. coli, L.monocytogenes, and S. enterica Typhimurium and the yeast C. albicans. The disk diffusion test showed a high inhibition potential against S. enterica compared to the standard antimicrobial tetracycline, as an inhibition index of 1.17 was found. For the other bacterial strains, the inhibition values were above 40%. The MIC test showed promising results in the inhibition of E. coli, L. monocytogenes, and C. albicans, indicating bacteriostatic activity against the first microorganism and bactericidal and fungicidal activities against the others. Therefore, the results showed the action of Na abietate as a possible effective antimicrobial drug, highlighting its sustainability within a circular economy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Green Synthesis of Na abietate Obtained from the Salification of Pinus elliottii Resin with Promising Antimicrobial Action

et al. 2023

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“…Finally, the quaternization of the alkyl bromide functionalities using trimethylamine resulted in the formation of water-soluble lipophilic cationic derivatives of different bile acids (BA-2/4 Hexyl, BA-3/4 Hexyl, and BA-4/4 Hexyl) with a quantitative yield (Figure B). The butyl group-bearing compounds were synthesized similarly as previously published . The library of the number of cationic charges (e.g., BA-2/4 Butyl: two charges, BA-3/4 Butyl: three charges, and BA-4/4 Butyl: four charges) allowed us to understand the SAR.…”

Section: Resultsmentioning

confidence: 99%

“…Since the facial arrangement can be beneficial by interacting with the EPS matrix in biofilms, which is composed of negatively charged polysaccharides, extracellular DNA, and proteins, we therefore explored the efficacy of bile acid-based antimicrobial agents in controlling chronic and recurrent infections associated with microbial biofilms and dormant microbial subpopulations. In the previous study, 34 the molecular architectures consist of a hydrophobic fused tetracyclic ring as the core with multiple butyl-or hexylcontaining quaternary ammonium charges as the head groups. These molecular designs exhibited ideal facial amphiphilicity since the cationic head groups are positioned at the convex-βface, whereas the hydrocarbon counterpart of the tetracyclic ring is oriented at the concave-α-face (Figure 1A,B).…”

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confidence: 99%

Facially Amphiphilic Bile Acid-Functionalized Antimicrobials: Combating Pathogenic Bacteria, Fungi, and Their Biofilms

et al. 2023

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We report facially amphiphilic bile acid-based antimicrobials with a broad spectrum of activity against both bacterial and fungal pathogens and negligible detrimental effects on mammalian cells. Two lead compounds eliminated dormant subpopulations of various bacterial species, unlike conventional antibiotics. The lead compounds were also effective in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. Additionally, these compounds substantially inhibited the formation of fungal biofilms (C. albicans). Mechanistic investigations revealed the membraneactive nature and endogenous reactive oxygen species (ROS) induction ability of these compounds. Finally, no detectable resistance was developed by the bacterial strains against this class of membrane-targeting antimicrobials.

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“…Meanwhile, long alkyl chains or bulky groups offer hydrophobicity. ,− For example, hydrophilic and hydrophobic groups are both designed as pendant groups with random arrangements or located in the same repeating unit. − Although some polymeric antibacterials exhibit desired performance against ordinary pathogens, one of the most challenging topics is how best to spatially arrange the cationic and hydrophobic residues of macromolecular antibacterials to form a “facially amphiphilic” structure to combat antibiotic-resistant bacteria. − Bile acids (BAs), derived from cholesterol and naturally stored in the gallbladder of mammals, have a rigid skeleton of steroids and have shown their potential in various therapeutic applications owing to their excellent biocompatibility. , The hydroxyl groups of BAs and polycyclic hydrocarbon structures are located on different surfaces of the rigid skeleton, forming a rare facially amphiphilic structure similar to AMPs and promoting a selective localization and penetration into bacterial membranes rather than mammalian cell membranes (Scheme A). In addition to easy availability and modifiability of BAs, BA-based antibacterials exhibited comparable bacterial killing abilities with antibiotics in vitro, confirming the superiority of facially amphiphilic skeletons of BAs as the building blocks to design antibacterials. − However, to mimic AMPs, transferring the facial amphiphilicity from unimolecule to macromolecule remains a great challenge until now.…”

Section: Introductionmentioning

confidence: 88%

Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides

Lin

Gao

et al. 2023

ACS Appl. Mater. Interfaces

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Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.

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Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy

Cited by 9 publications

References 50 publications

Green Synthesis of Na abietate Obtained from the Salification of Pinus elliottii Resin with Promising Antimicrobial Action

Green Synthesis of Na abietate Obtained from the Salification of Pinus elliottii Resin with Promising Antimicrobial Action

Facially Amphiphilic Bile Acid-Functionalized Antimicrobials: Combating Pathogenic Bacteria, Fungi, and Their Biofilms

Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides

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