Spontaneous cyclization of 2-methylthiosemicarbazones yields new 1,2,4-triazolidine-3-thiones, useful as building blocks for drug design

Gričar, Simona (author), Počkaj, Marta (author), Marolt, Gregor (author), Škaro Bogojević, Sanja (author), Novinec, Marko (author), Kljun, Jakob (author)

From the point of view of medicinal chemistry, thiosemicarbazones are interesting molecules as they exhibit various biological activities, such as antitumor, antifungal, antibacterial, antiviral, and antileukemic properties, and their synthesis is deeply investigated. However, the synthesis using 2-methylthiosemicarbazide as a starting compound to prepare new 1,2,4-triazolidine-3-thione compounds via 2-methylthiosemicarbazone cyclization has not been reported yet. Therefore, fifteen new 1,2,4-triazolidine-3-thione compounds were synthesized during a cyclization reaction using a simple green procedure with minimal use of hazardous solvents. The synthesized compounds were characterized with the techniques of NMR, IR, MS, and CHN elemental analysis. In addition, the structure of 11 of these compounds was confirmed by X-ray structure determination. Selected compounds were subjected to cytotoxicity assay and microbiological tests for antimicrobial susceptibility and quorum sensing inhibition and tested for their inhibitory effect on the metalloenzyme NDM-1, which causes antimicrobial resistance.

• Language: English
• Keywords: 2-methylthiosemicarbazide, 1, 2, 4-triazolidine-3-thiones, cyclization, green chemistry, NDM-1
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 10 str.
• Numbering: Vol. 10, iss. 2, art. e202404001
• PID: 20.500.12556/RUL-166470
• UDC: 547.288.3:66.095.25
• ISSN on article: 2365-6549
• DOI: 10.1002/slct.202404001
• COBISS.SI-ID: 222062339
• Publication date in RUL: 14.01.2025

Record is a part of a journal

• Title: ChemistrySelect
• Publisher: Wiley, Chemistry Europe
• ISSN: 2365-6549
• COBISS.SI-ID: 5855514

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.

Secondary language

• Language: Slovenian
• Keywords: 2-metiltiosemikarbazid, 1, 2, 4-triazolidin-3-tioni, ciklizacija, zelena kemija, NDM-1