Applied Chemical Engineering

Synthesis of triclosan-derived coumarins as potent, biocompatible, broad-spectrum antimicrobial agents

Marwa Mohammed Alshaher

Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq

Yasser Fakri Mustafa

Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq

DOI: https://doi.org/10.59429/ace.v7i4.5579

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Abstract

Objective:  Various personal care products previously used triclosan, a chlorinated antimicrobial agent. However, safety and environmental concerns have grown, forbidding its application. Given this fact, the present work aims to repurpose this out-of-use chemical by including it as a precursor for synthesizing nineteen triclosan-based coumarins (TBCs). Methods: The spectrophotometric methods applied to confirm the chemical structures of TBCs were FTIR, ¹H-NMR, ¹³C-NMR, and HRMS. The antimicrobial investigations were run through using broth microdilution methodology and many pathogenic microbes. These include six aerobic and four anaerobic ATCC-approved bacterial strains, as well as two fungal strains. We validated the results by comparing them with three standards: ciprofloxacin, metronidazole, and nystatin, which were based on the tested microbe. On the other hand, the biocompatibility investigations determined the ability of TBCs to inhibit the normal growth of three microbiome strains. Results: The results revealed several conclusive points, including the bactericidal impact of the synthesized TBCs on both pathogenic and microbiome strains tested, with low and high MIC values, respectively. The impact of the synthesized TBCs on pathogenic bacteria was dependent on the number and type of substitutes on the D ring, but this was not the case for microbiome bacteria, where these two factors were of low importance. These factors also influence the activity of the synthesized TBCs against pathogenic fungi. The latter microbes exhibit a high level of sensitivity to the synthetic intermediate, which contains a carboxylic acid moiety within its structure. We concluded from these findings that the number of chlorides that deactivated the D ring directly promoted the anti-aerobic bacterial activity. The same holds true for the anti-anaerobic bacteria, albeit with the addition of nitro groups. Conclusion: the results could provide insights into how the structure of the synthesized TBCs influences their antimicrobial activity. This renders them highly promising as potential future medicines that are robust, safe, and effective against a broad spectrum of microbes.

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