Synthesis and biofilm inhibitory activity of cyclic dinucleotide analogues prepared with macrocyclic ribose-phosphate skeleton

Di Xie; Lingyun Xu; Shuwei Yuan; Jiayin Yan; Peng Zhou; Wenpei Dong; Jinliang Ma; Changpo Chen

doi:10.1016/j.bmcl.2025.130107

Synthesis and biofilm inhibitory activity of cyclic dinucleotide analogues prepared with macrocyclic ribose-phosphate skeleton

Bioorg Med Chem Lett. 2025 Jan 17:130107. doi: 10.1016/j.bmcl.2025.130107. Online ahead of print.

Authors

Di Xie¹, Lingyun Xu¹, Shuwei Yuan¹, Jiayin Yan¹, Peng Zhou¹, Wenpei Dong¹, Jinliang Ma², Changpo Chen³

Affiliations

¹ Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China.
² Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China. Electronic address: [email protected].
³ Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China. Electronic address: [email protected].

PMID: 39828003
DOI: 10.1016/j.bmcl.2025.130107

Abstract

Cyclic diguanosine monophosphate (c-di-GMP) is the key second messenger regulating bacterial biofilm formation related genes. Several c-di-GMP analogues have demonstrated biofilm inhibition activity. In this study, ribose-phosphate macrocyclic skeleton containing 1'-azido groups was constructed, and CDN analogues were prepared via click chemistry. The biofilm formation inhibition activity of the analogues was evaluated, and compound 17 illustrated better activity than c-di-GMP. This high-throughput strategy could be extended to synthesize cyclic analogues for biological research and immunotherapeutic development.

Keywords: Biofilm inhibition; Macrocyclic ribose-phosphate skeleton; Triazole; c-di-GMP.