Synthetic Strategies and Biological Activities of Teixobactin and its Analogs: A Review

Curr Top Med Chem. 2025 Jan 7. doi: 10.2174/0115680266344835241125074030. Online ahead of print.

Abstract

Antibiotics are a revolutionary discovery in modern medicine, enabling the successful treatment of bacterial infections that were once untreatable and deadly. Teixobactin, a "head-toside- chain" cyclodepsipeptide, shows great promise as a lead compound for developing new antibiotics to deal with multi-drug-resistant bacterial infections. The unique pharmacological profile and intriguing structural characteristics of teixobactin, including its unusual amino acid residues (three D-amino acids and L-allo-enduracididine), have drawn the attention of multiple research groups seeking to create new antibiotics with innovative mechanisms. This review explores recent developments in the chemical structure of teixobactin, its biological role in cells, its biosynthetic production pathway, and how it disrupts bacteria (mode of action). Along with the structureactivity relationship (SAR) studies, this review also covers various synthetic approaches used to create teixobactin and its analogs. Finally, some observations regarding emerging patterns during the synthesis of unique analogs of teixobactin, as well as suggestions for further research and developments, are discussed.

Keywords: L-allo-Enduracididine; Teixobactin; biological activity.; cyclodepsipeptide; ichip technology.