Organoruthenium(II) complexes of acetazolamide potently inhibit human carbonic anhydrase isoforms I, II, IX and XII

Abstract

Two acetazolamide (AAZ) complexes with ruthenium(II) η6-p-cymene chloride were synthesised, characterised and tested for their inhibitory effects on several carbonic anhydrase (CA, EC 4.2.1.1) isoforms with pharmacological applications. Against human (h) isoform hCA I, the two complexes showed inhibition constants in the range of 8.5–23.4 nM (AAZ has a KI of 250 nM), against hCA II of 0.48–4.2 nM, whereas against hCA IX of 0.63–3.8 nM and against hCA XII of 0.04–0.52 nM, respectively. These highly effective ruthenium acetazolamide derivatives against the tumour-associated CA isoforms IX and XII warrant further in vivo studies, in hypoxic tumours overexpressing these enzymes.

Keywords

• carbonic anhydrase
• human isoforms
• acetazolamide
• ru(ii)
• metal complex