3,1-Benzothiazines, 1,4-benzodioxines, 1,4-benzoxazines as inhibitors of matriptase-2 : outcome of a focused screening approach

Roydeva, Polya G. (author), Beckmann, Anna-Madeleine (author), Stirnberg, Marit (author), Cesar, Jožko (author), Kikelj, Danijel (author), Ilaš, Janez (author), Gütschow, Michael (author)

The liver enzyme matriptase-2 is a multi-domain, transmembrane serine protease with an extracellular, C-terminal catalytic domain. Synthetic low-molecular weight inhibitors of matriptase-2 have potential as therapeutics to treat iron overload syndromes, in particular in patients with β-thalassemia. A sub-library of 64 compounds was screened for matriptase-2 inhibition and several active compounds were identified. (S)-Ethyl 2-(benzyl(3-((4-carbamidoylphenoxy)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-2-oxoacetate ((S)-12) showed an IC$_{50}$ value of less than 10 µM. Structure-activity relationships were discussed and proposals to design new matriptase-2 inhibitors were made.

• Language: English
• Keywords: marine alkaloid, Agelas, clathrodin, oroidin, pyrrole-2-aminoimidazole, antibacterial, benzamidines, 4H-3, 1-benzothiazin-4-ones, 2, 3-dihydro-1, 4-benzodioxines, 3, 4-dihydro-2H-1, 4-benzoxazines, matriptase-2, protease inhibition
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2016
• Number of pages: 11 str.
• Numbering: Vol. 9, iss. 1, art. 2
• PID: 20.500.12556/RUL-130387
• UDC: 543:615.2
• ISSN on article: 1424-8247
• DOI: 10.3390/ph9010002
• COBISS.SI-ID: 4018289
• Publication date in RUL: 14.09.2021

Record is a part of a journal

• Title: Pharmaceuticals
• Shortened title: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

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: 01.03.2016

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: German Research Foundation (DFG)
• Project number: STI 660/1-1

• Funder: Other - Other funder or multiple funders
• Funding programme: University of Bonn, Gender Equality Center, Maria von Linden Program