Targeting SIRT2 with Oxadiazole/Thiadiazole-Based Acetamides: <i>In Silico</i> Screening and <i>In Vitro</i> Cytotoxicity Evaluation

Aksel A. B., GÖZELLE M., BAKAR ATEŞ F., ÖZKAN Y., Ozkan E., EREN G.

POLYCYCLIC AROMATIC COMPOUNDS, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1080/10406638.2025.2562259
  • Dergi Adı: POLYCYCLIC AROMATIC COMPOUNDS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Computer & Applied Sciences, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Karadeniz Teknik Üniversitesi Adresli: Hayır

Özet

As a key member of the human sirtuin family, Sirtuin 2 (SIRT2) is crucial in orchestrating numerous biological processes, such as cell cycle regulation, apoptosis, and metabolic homeostasis, and has emerged as a promising biomarker for various conditions, particularly neurodegenerative diseases, and cancer. Given the growing therapeutic interest focused toward SIRT2 inhibition, we have synthesized a series of 1,3,4-oxadiazole/thiadiazole-2-arylthioacetamides featuring 2-/3-substituted benzyl or pyrimidin-2-ylmethyl at the 5th position of the oxadiazole/thiadiazole ring, to evaluate their potential as SIRT2 inhibitors. Among the compounds synthesized, ST95 displayed selective inhibitory activity against SIRT2 with an IC50 value of 10.62 mu M and inhibited the growth of MCF-7 (IC50 = 111.10 mu M) and LNCaP (IC50 = 14.69 mu M) cancer cell lines, highlighting its potential as a lead compound for further development.