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Synthesis and Evaluation of Spumigin Analogues Library with Thrombin Inhibitory Activity.

ABSTRACT: Spumigins are marine natural products derived from cyanobacteria Nodularia spumigena, which mimics the structure of the d-Phe-Pro-Arg sequence and is crucial for binding to the active site of serine proteases thrombin and factor Xa. Biological evaluation of spumigins showed that spumigins with a (2S,4S)-4-methylproline central core represent potential lead compounds for the development of a new structural type of direct thrombin inhibitors. Herein, we represent synthesis and thrombin inhibitory activity of a focused library of spumigins analogues with indoline ring or l-proline as a central core. Novel compounds show additional insight into the structure and biological effects of spumigins. The most active analogue was found to be a derivative containing l-proline central core with low micromolar thrombin inhibitory activity.

SUBMITTER: Zula A

PROVIDER: S-EPMC6266488 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Spumigin Analogues Library with Thrombin Inhibitory Activity.

Žula Aleš A Będziak Izabela I Kikelj Danijel D Ilaš Janez J

Marine drugs 20181027 11

Spumigins are marine natural products derived from cyanobacteria Nodularia spumigena, which mimics the structure of the d-Phe-Pro-Arg sequence and is crucial for binding to the active site of serine proteases thrombin and factor Xa. Biological evaluation of spumigins showed that spumigins with a (2S,4S)-4-methylproline central core represent potential lead compounds for the development of a new structural type of direct thrombin inhibitors. Herein, we represent synthe ...[more]

PMID: 30373260

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