New bis- and tetrakis-1,2,3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants

NURAL Y., ÖZDEMİR S., Yalcin M. S., DEMİR B., Atabey H., SEFEROĞLU Z., ...Daha Fazla

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, cilt.55, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 55
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.bmcl.2021.128453
  • 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, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Bis, Triazole, Tetrakis, Triazole, DNA-cleavage, Molecular docking, Antioxidant, Antimicrobial, Acid dissociation constant, BIS-1,2,3-TRIAZOLE DERIVATIVES, BIOLOGICAL EVALUATION, CRYSTAL-STRUCTURE, IN-VITRO, 1,2,3-TRIAZOLE, ANTICANCER, COMPLEXES, LIGANDS, BINDING, DESIGN
  • Gazi Üniversitesi Adresli: Evet

Özet

In this study, a series of bis- and tetrakis-1,2,3-triazole derivatives were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry in 73-95% yield. The bis- and tetrakis-1,2,3-triazoles exhibited significant DNA cleavage activity while the tetrakis-1,2,3-triazole analog 6g completely degraded the plasmid DNA. Molecular docking simulations suggest that compound 6g acts as minor groove binder of DNA by binding through several noncovalent interactions with base pairs. All bis- and tetrakis-1,2,3-triazole derivatives were screened for antibacterial activity against E. coli, B. cereus, S. aureus, P. aeruginosa, E. hirae, L. pneumophila subsp. pneumophila strains and antifungal activity against microfungus C. albicans and C. tropicalis strains. Compound 4d exhibited the best antibacterial activity among bis-1,2,3-triazoles against E. coli and E. hirae, while 6c exhibited the best antibacterial activity among tetrakis-1,2,3-triazoles against E. hirae. Furthermore, the best antifungal activity against C. albicans and C. tropicalis was reported for the compound 5, while 6d displayed the best antifungal activity against C. tropicalis and C. albicans. Reasonable iron chelating activities and DPPH radical scavenging abilities were found for some of the compounds. Finally, the acid dissociation constants (pKa) of the bis-1,2,3-triazoles were also determined with the help of HYPERQUAD program using the data obtained from potentiometric titrations. The reported data here concludes that the bis- and tetrakis-1,2,3triazoles are important cores that should be considered for further development of especially new anticancer agents acting through the DNA cleavage activity.