Novel 4-Bromobenzyl-1H-1,2,3-Triazole Scaffold for Multi-target Enzyme Inhibition in Helicobacter Gastric Injury via Experimental and Computational Approaches
Journal of Pharmaceutical Innovation, cilt.21, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 21 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s12247-025-10298-9
- Dergi Adı: Journal of Pharmaceutical Innovation
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, INSPEC
- Anahtar Kelimeler: 1,2,3-triazole, Gastric ulcer, Helicobacter pylori, Molecular dynamics, Multi-target enzyme inhibition, Urease inhibition
- Gazi Üniversitesi Adresli: Evet
Özet
Regioselective elaboration of a 4-bromobenzyl-1H-1,2,3-triazole scaffold was achieved through a concise, metal-free sequence that preserves the C-4 carboxylate as a metal-coordinating handle while diversifying the C-5 position. Thermal azide–alkyne cycloaddition between 1-(azidomethyl)-4-bromobenzene and dimethyl but-2-ynedioate furnished the 4,5-diester core, followed by LTBA-mediated, chemoselective reduction of the C-5 ester to an aldehyde at − 10 °C in THF. Modular condensation of the aldehyde delivered three derivatives—Schiff base (a2), hydrazone (a3), and benzimidazole (a1)—in 95–98% yields, with structures confirmed by NMR and HRMS. The regioselective design maximized metal coordination (Ni²+, Zn²+, Fe³+) and produced multi-target inhibition against urease, collagenase, and 15-LOX; the imine derivative a2 was most potent (IC50: 7.21 µM, 27.36 µM, 2.76 µM, respectively), consistent with docking, MD, and MM/GBSA analyses. This synthesis-first strategy establishes a privileged, polypharmacological platform for gastric-injury targets.