Design and synthesis of novel 3-triazolyl-1-thiogalactosides as galectin-1, -3 and -8 inhibitors

van Klaveren, Sjors (author), Dernovšek, Jaka (author), Jakopin, Žiga (author), Anderluh, Marko (author), Leffler, Hakon (author), Nilsson, Ulf (author), Tomašič, Tihomir (author)

Galectins are galactoside-binding proteins that play a role in various pathophysiological conditions, making them attractive targets in drug discovery. We have designed and synthesised a focused library of aromatic 3-triazolyl-1-thiogalactosides targeting their core site for binding of galactose and a subsite on its non-reducing side. Evaluation of their binding affinities for galectin-1, -3, and -8N identified acetamide-based compound 36 as a suitable compound for further affinity enhancement by adding groups at the reducing side of the galactose. Synthesis of its dichlorothiophenyl analogue 59 and the thiodigalactoside analogue 62 yielded promising pan-galectin inhibitors.

• Language: English
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: str. 18973-18984
• Numbering: Vol. 12, iss. 29
• PID: 20.500.12556/RUL-137879-ad0f6b22-48a5-5fc0-5f37-8a6f84036551
• UDC: 615.4:54(057)
• ISSN on article: 2046-2069
• DOI: 10.1039/D2RA03163A
• COBISS.SI-ID: 113857283
• Publication date in RUL: 05.07.2022

Record is a part of a journal

• Title: RSC advances
• Publisher: Royal Society of Chemistry
• ISSN: 2046-2069
• COBISS.SI-ID: 2513252

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: 05.07.2022

Secondary language

• Language: Slovenian
• Keywords: β-galaktozid, galektini, raziskava zdravil, diklorotiofenilni analog 59