Synthesis, characterization, and biological evaluation of novel cinnamic acid derivatives: cinnamoyl-metronidazole ester and cinnamoyl-memantine amide

Abstract

In this study, two derivatives, namely the ester derivative cinnamoyl metronidazole and the amide derivative cinnamoyl memantine, were synthesized from cinnamic acid and respective drugs for the purpose of exploring their potential as novel and efficient antimicrobial agents in the quest of prevailing the global antimicrobial resistance challenge.The synthesis process involved two steps: first, the chlorination of cinnamic acid using thionyl chloride, and second, the esterification of metronidazole or the amidation of memantine. These steps resulted in the formation of cinnamoyl metronidazole/memantine. Optimal reaction conditions were established, and chromatographic techniques were used to separate the synthesized compounds. Confirmation of successful synthesis was achieved through FT-IR analysis, which readily distinguished the chlorinated product and derivatives based on distinctive bands, including mainly the one of carbonyl group. Additionally, molecular structures were validated using 1H NMR and 13C NMR, with all peaks further confirming the successful esterification/amidation of cinnamoyl and drug moieties.Upon evaluating the biological activity, the parent compounds exhibited negligible effects within the tested concentration range. However, the derivatives demonstrated significant activity. The ester derivative exhibited potent activity against the Gram-positive bacterium Staphylococcus aureus, as evidenced by a zone of inhibition measuring 12–15 mm in diameter. Conversely, the amide derivative displayed appreciable biological activity against Candida fungi, with an inhibition zone measuring 11–14 mm.

Keywords

• Cinnamic acid
• Cinnamoyl chloride
• Memantine
• Metronidazole
• Antibacterial
• Antifungal