Synthesis and evaluation of spumigin analogues library with thrombin inhibitory activity

Žula, Aleš (author), Będziak, Izabela (author), Kikelj, Danijel (author), Ilaš, Janez (author)

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.

• Language: English
• Keywords: marine products, natural peptides, peptidomimetics, thrombin inhibition
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2018
• Number of pages: 20 str.
• Numbering: Vol. 16, iss. 11, art. 413
• PID: 20.500.12556/RUL-125357
• UDC: 577
• ISSN on article: 1660-3397
• DOI: 10.3390/md16110413
• COBISS.SI-ID: 39787781
• Publication date in RUL: 12.03.2021

Record is a part of a journal

• Title: Marine drugs
• Shortened title: Mar. drugs
• Publisher: MDPI
• ISSN: 1660-3397
• COBISS.SI-ID: 23578841

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 12.03.2021

Secondary language

• Language: Slovenian
• Keywords: biokemija, morski proizvodi, naravni peptidi, inhibicija trombina

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: EC - European Commission
• Funding programme: FP7
• Project number: 245137
• Name: Exploring Marine Resources for Bioactive Compounds: From Discovery to Sustainable Production and Industrial Applications
• Acronym: MAREX