Novel Re(I) tricarbonyl coordination compounds based on 2-pyridyl-123-triazole derivatives bearing a 4-amino-substituted benzenesulfonamide arm: synthesis crystal structure computational studies and inhibitory activity against carbonic anhydrase I II and IX isoforms†

摘要

In this work, two bidentate 2-pyridyl-1,2,3-triazole ligands (>3a and >3b) containing a 4-substituted benzenesulfonamide pharmacophore prepared by classical click chemistry procedures, as well as their corresponding rhenium complexes, >4a and >4b of general formula [ReCl(CO)3(>L)] (>L => 3a or >3b) were prepared and fully characterised by spectroscopic methods (IR, NMR, MS, UV-Vis), elemental analysis, X-ray diffraction, and theoretical studies using DFT and TD-DFT methods. In particular, we showed that, in the solid state, the pyridine and the triazole rings of >3b adopted an uncommon cis configuration which stems from intermolecular hydrogen bonds. Preliminary assays demonstrated a promising nanomolar inhibitory activity against carbonic anhydrase isoform IX for both ligands and complexes with a strong affinity Ki of 2.8 nM for ligand >3a. More interestingly, complex >4b exhibited a pronounced selectivity against hCA IX over the off-targets hCA I and hCA II which makes this compound a promising potential anticancer drug candidate.