10th Asian Biological Inorganic Chemistry Conference

Abstract

<p>Hinokitiol, a molecule naturally isolated from essential oil of cypress tree, exhibits anti-microbial, anti-fungal, anti-inflammatory, and anti-viral activity, therefore has been widely applied in industry.¹ Moreover, due to its metal-chelating property, it is also called a metallophore, which can form metal complexes.</p><p>In this study, we proposed that hinokitiol chelates with bismuth(III) to form a complex, leading to enhanced antimicrobial activity. A series of thujaplicins derivatives (i.e., hinokitiol and tropolone-related) were synthesized and the combination of bismuth with these ligands were examined against six <em>Staphylococcus aureus</em> strains, including MRSA strains. Most of the combinations exhibited synergism (FIC values of less than 0.5) upon treating bacterial strains. We also rationalized the structure-activity-relationship (SAR) and found that their antimicrobial activities correlate with both lipophilicity and binding affinity. Moreover, combinatorial hinokitiol and CBS exhibited anti-biofilm activity by preventing biofilm formation, and also killed <em>S. aureus</em> persister cells. Detailed antimicrobial activities of these complexes <em>in vivo</em> and the mechanistic insights were examined by multiple omics approaches together with bioassay, and will be discussed.</p>