Journal
NEW JOURNAL OF CHEMISTRY
Volume 45, Issue 27, Pages 11937-11945Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1nj00776a
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Funding
- Science and Engineering Research Board, Government of India [CRG/2019/003462]
- SASTRA Deemed University [R&M/0021/SCBT 007/201213]
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The introduction of new cationic N-acylethanolamines showed promising antimicrobial activity against Mycobacterium smegmatis, with the minimum inhibitory concentration decreasing as the N-acyl chain length increased. Additionally, cNAEs in combination with isoniazid exhibited synergistic activity by disrupting bacterial membrane, generating reactive oxygen species, and depolarizing the membrane. Hemolytic study confirmed that cN16E is non-toxic to human red blood cells.
The emergence of drug-resistant microorganisms and the failure of conventional antibiotics demand extensive research efforts to develop more effective antimicrobial therapies. A new series of cationic N-acylethanolamines was synthesized through introducing a (2-methylene-1-methylpyridinium iodide) moiety, and their antimicrobial activity was evaluated against Mycobacterium smegmatis. The minimum inhibitory concentration (MIC) of cNAEs follows a fourfold decrement when the N-acyl chain length increases by two methylene units. Inspiringly, the lowest MIC of 15.63 mu M was observed with 2-((N-(2-hydroxyethyl)palmitamido)methyl)-1-methylpyridin-1-ium iodide, suggesting the necessity of a hydrophilic-lipophilic balance for better antimicrobial activity. cNAEs are unique, because they do not produce reactive oxygen species as most antibiotics do, but exert antimicrobial activity through loss of membrane integrity and membrane depolarization. Further, cNAEs and their combination with a standard drug, isoniazid, exhibit synergistic activity at lower concentrations (cN16E/INH - 3.91/1.95 mu M) in comparison to the MIC of the individual drug. Strikingly, the combination showed a bactericidal effect through bacterial membrane disruption, ROS generation and membrane depolarization. Notably, a hemolytic study showed that cN16E is nontoxic to human red blood cells, even above 100 fold higher MIC. The result signifies that cN16E can be used as a potential drug against mycobacteria, as well as in combination with other antimycobacterial drugs.
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