Skeen Tyler L, Gresham Rebekah L, Agamaite Katherine A, Molz Olivia M, Westlake Isabelle F, Kregenow Sage M, Romero Al K, Flood Brian M, Mazur Lauren E, Hinkle Robert J, Young Douglas D
Department of Chemistry, William & Mary, Williamsburg, VA 23185, USA.
Molecules. 2024 Dec 17;29(24):5945. doi: 10.3390/molecules29245945.
The development of new antibiotics with unique mechanisms of action is paramount to combating the growing threat of antibiotic resistance. Recently, based on inspiration from natural products, an asymmetrical polyacetylene core structure was examined for its bioactivity and found to have differential specificity for different bacterial species based on the substituents around the conjugated alkyne. This research further probes the structural requirements for bioactivity through a systematic synthesis and investigation of new compounds with variable carbon chain length, alkynyl subunits, and alcohol substitution. Furthermore, the research examines the activity of the new compounds towards the inhibition of biofilm formation. Overall, several key new polyyne compounds have been identified in both decreasing bacterial viability and in disrupting pre-formed biofilms. These properties are key in the fight against bacterial infections and will be helpful in the further development of new antibiotic agents.
开发具有独特作用机制的新型抗生素对于应对日益严重的抗生素耐药性威胁至关重要。最近,基于从天然产物中获得的灵感,研究了一种不对称聚乙炔核心结构的生物活性,发现基于共轭炔周围的取代基,其对不同细菌物种具有不同的特异性。这项研究通过系统合成和研究具有可变碳链长度、炔基亚基和醇取代的新化合物,进一步探究了生物活性的结构要求。此外,该研究还考察了新化合物对生物膜形成的抑制活性。总体而言,已鉴定出几种关键的新型聚炔化合物,它们既能降低细菌活力,又能破坏预先形成的生物膜。这些特性是对抗细菌感染的关键,将有助于新型抗生素药物的进一步开发。