Abstract
Due to overuse and/or misuse of antibiotics, antimicrobial resistance (AMR) has emerged to be a big threat to human and animal health. Developing new antimicrobial agents is becoming more urgent than ever along with increased appearance of antimicrobial resistant bacteria. We initiated a novel approach to reduce AMR development by chemically linking synergistic antibiotics and phytochemicals. Our first conjugate, sulfamethoxazole-gallic acid (Hybrid 1), was only effective towards Streptococci and Enterococci. To improve antimicrobial activity and bacterial susceptibility, we designed and synthesized four new conjugates, sulfamethoxazole-eugenol, sulfamethoxazole-protocatechuic acid, sulfamethoxazole-vanillic acid and sulfamethoxazole-caffeic acid. Compared to Hybrid 1, these four conjugates exhibited stronger antimicrobial activities towards all six tested Gram-positive and one tested Gram-negative bacteria. This implicates that synthesis of antibiotic-phytochemical conjugates is a promising strategy in developing novel antimicrobial agents.
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