Synthesis of novel immunomodulatory 1,4-disubstituted bis-1,2,3-triazoles by using click chemistry and their intracellular mechanism of action

NURAL Y., Acar I., Yetkin D., Efeoglu C., SEFEROĞLU Z., AYAZ F.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, cilt.69, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 69
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.bmcl.2022.128800
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Click chemistry, Immunomodulatory activity, Anti-inflammatory activity, PI3K pathway, Bis-1, 2, 3-triazole, ACID DISSOCIATION-CONSTANT, BIOLOGICAL EVALUATION, 1,2,3-TRIAZOLES, INFLAMMATION, INHIBITORS
  • Gazi Üniversitesi Adresli: Evet

Özet

In this study, six new 1,4-disubstituted bis-1,2,3-triazole compounds, N,N '-(1,2-phenylene)bis(2-(4-R-1H-1,2,3triazol-1-yl)acetamide), were synthesized with high yield (88-96 %) by using click chemistry and their molecular structures were characterized by using NMR, FT-IR, HRMS and elemental analysis techniques. Previous studies suggest anti-inflammatory and analgesic activities for different 1,2,3-triazole derivatives and in the light of those studies we aimed to examine these novel derivatives immunomodulatory activities on the mammalian macrophages. Pro-inflammatory cytokines (TNF, IL6, GMCSF and IL12p40) secretion levels were tested in the presence of bis-1,2,3-triazole compounds when the macrophages were activated with LPS. These new derivatives were able to suppress the production of these cytokines at different levels. Intracellular phophorylated PI3K protein levels were measured due to its prominent role in inflammatory reactions. Our flow cytometry analysis results suggested that some of these compounds were partially effective through PI3K pathway. In different inflammatory and autoimmune disease settings these novel 1,2,3-triazole derivatives can be utilized as non-steroid based anti-inflammatory drug candidates.