Novel 4-Bromobenzyl-1<i>H</i>-1,2,3-Triazole Scaffold for Multi-target Enzyme Inhibition in <i>Helicobacter</i> Gastric Injury via Experimental and Computational Approaches
Akkar, Mehmet Eren, Ortaakarsu, Ahmet Bugra, Boga, Ozlem Bakir, Kurbanoglu, Esabi Basaran, Altundas, Aliye
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 degrees 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 (Ni-2+, Zn-2+, Fe-3+) and produced multi-target inhibition against urease, collagenase, and 15-LOX; the imine derivative a2 was most potent (IC50: 7.21 mu M, 27.36 mu M, 2.76 mu M, respectively), consistent with docking, MD, and MM/GBSA analyses. This synthesis-first strategy establishes a privileged, polypharmacological platform for gastric-injury targets.
- Dergi
- JOURNAL OF PHARMACEUTICAL INNOVATION
- Yıl
- 2025
- Cilt
- 21
- Sayı
- 1
- ISSN
- 1872-5120
- eISSN
- 1939-8042
- DOI
- 10.1007/s12247-025-10298-9
- WoS UID
- WOS:001648975200001