Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA.
Center for Biofilm Engineering, Montana State University, Bozeman, MT, USA.
Chem Biol Drug Des. 2021 Jan;97(1):134-147. doi: 10.1111/cbdd.13768. Epub 2020 Sep 22.
Prodrugs are pharmacologically attenuated derivatives of drugs that undergo bioconversion into the active compound once reaching the targeted site, thereby maximizing their efficiency. This strategy has been implemented in pharmaceuticals to overcome obstacles related to absorption, distribution, and metabolism, as well as with intracellular dyes to ensure concentration within cells. In this study, we provide the first examples of a prodrug strategy that can be applied to simple phenolic antimicrobials to increase their potency against mature biofilms. The addition of (acetoxy)methyl iminodiacetate groups increases the otherwise modest potency of simple phenols. Biofilm-forming bacteria exhibit a heightened tolerance toward antimicrobial agents, thereby accentuating the need for new antibiotics as well as those, which incorporate novel delivery strategies to enhance activity toward biofilms.
前药是药物的药理减效衍生物，一旦到达靶位，就会通过生物转化为活性化合物，从而最大限度地提高其效率。这一策略已在制药领域得到应用，以克服与吸收、分布和代谢相关的障碍，以及与细胞内染料一起确保细胞内的浓度。在这项研究中，我们提供了前药策略的第一个例子，该策略可应用于简单的酚类抗菌药物，以提高其对成熟生物膜的效力。（乙酰氧基）甲基亚氨基二乙酸酯基团的添加增加了原本温和的简单酚类的效力。形成生物膜的细菌对抗菌药物表现出更高的耐受性，从而强调了对新抗生素的需求，以及那些采用新的输送策略来提高对生物膜活性的抗生素的需求。
