New Coumarin-Metronidazole Composites: Synthesis, Biocompatibility, and Anti-anaerobic Bacterial Activity

• Published in: Russian journal of bioorganic chemistry 2024-02, Vol.50 (1), p.201-210
• Main Author: Mustafa, Yasser Fakri
• Format: Article
• Language: English
• Subjects: Acetic acid; Bacteria; Biochemistry; Biocompatibility; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Chemical compounds; Chemical reactions; Chemical synthesis; Composite materials; Conjugation; Coumarin; Dilution; Esterification; Life Sciences; NMR; Nuclear magnetic resonance; Organic Chemistry; Precursors; Spectrophotometers
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S106816202401014X

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, 1 H NMR, and 13 C 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.