Bis(carbamoyl)benzoic Acids from TMACl: Evaluation as Antibacterial and Anti-Giardia Agents

Abstract

Bacterial resistance and parasitic infections like giardiasis remain major public health challenges, driving the need for new therapeutic agents. This study reports the synthesis and biological evaluation of 17 bis(carbamoyl)benzoic acids derived from trimellitic anhydride chloride (TMACl), a largely unexplored monomer typically used in polymer chemistry. The compounds were synthesized by reacting TMACl with various amines, yielding high purity and excellent yields (81%–99%). Antimicrobial activity was assessed against clinically relevant bacteria (Enterococcus faecalis, Staphylococcus aureus, MRSA, Pseudomonas aeruginosa, and Escherichia coli) and the protozoan Giardia intestinalis. Eight compounds (3a–3e, 3g, 3h, and 3k) showed antibacterial activity (MIC = 25–200 µg/mL), with 3k being the most effective, particularly against E. faecalis (25 µg/mL), S. aureus (100 µg/mL), and MRSA (200 µg/mL). Compounds 3f–3j, 3n, 3p, and 3q exhibited anti-Giardia activity, with 3h being the most potent (IC₅₀ = 37.7 µg/mL). Toxicological assessment via in silico prediction and in vivo testing in BALB/c mice revealed no acute toxicity at 300 mg/kg (Category IV), well above the active concentrations. To our knowledge, this is the first report on the biological activity of TMACl-derived bis(carbamoyl)benzoic acids, with 3h and 3k emerging as promising leads for novel antimicrobial development.