Abstract
ctive: In light of their diverse molecular features and wide range of biological activities, compounds with coumarin-based chemical structures have drawn significant scientific interest. On the other hand, despite the massive development of anti-aerobic bacterial agents, those that fight anaerobic bacteria are less advanced. Methods: In this work, 3-halomequinol derivatives were condensed via a Pechmann coupling reaction with 3-oxopentanedioic acid, affording precursors named 7-halo-6-methoxycoumarin-4-acetic acids and coded (P1–P4). These were esterified with metronidazole by thionyl chloride to give the four new coumarin-metronidazole composites coded (COU–MTZ1–COU–MTZ4). The structural conformation of these composites and their corresponding precursors was determined by analyzing the spectra acquired from FT-IR, 1H NMR, and 13C NMR spectrophotometers. The anti-anaerobic bacterial activity was assessed by determining the composites’ inhibitory impact against four strains of pathogenic bacteria using broth dilution as a methodology. The biocompatibility profiles of the synthesized composites were spotlighted by in vitro inspection as well as by following their effects on the cellular growth of two normal-type bacterial strains and three healthy-type cell lines. Finally, the possibility of the composites being drug candidates was checked in silico by calculating their pharmacokinetic and drug-like attributes. Results: The results indicated that the new composites are biocompatible and demonstrated improved activity relative to the reference, with a golden effect attributed to the flouro-based composite. Discussion: This work reports the success in the synthesis and characterization of four (COU–MTZ) composites and their precursors. The synthetic composites showed more promising anti-anaerobic bacterial activity than the parent drug, with better theoretical aqueous solubility, intestinal absorption, and association with plasma proteins. Concerning the biocompatibility study, the synthetic composites did not demonstrate any obvious negative impact on the cellular growth of two normal-type bacterial strains and three healthy-type cell lines. Conclusions: It is concluded that the conjugation of metronidazole with the synthesized coumarins can improve its lipophilicity and consequently the candidate’s penetration into the test anaerobic pathogens, affording a promising synthon template for advanced research.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The author is very grateful to the University of Mosul/College of Pharmacy for their provided facilities, which helped to improve the quality of this work.
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Mustafa, Y.F. New Coumarin-Metronidazole Composites: Synthesis, Biocompatibility, and Anti-anaerobic Bacterial Activity. Russ J Bioorg Chem 50, 201–210 (2024). https://doi.org/10.1134/S106816202401014X
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DOI: https://doi.org/10.1134/S106816202401014X