[(Cp‐R)M(CO)₃] (M=Re or ^99mTc) Arylsulfonamide, Arylsulfamide, and Arylsulfamate Conjugates for Selective Targeting of Human Carbonic Anhydrase IX

Abstract

Enhanced receptor selectivity: carbonic anhydrase inhibitors are relevant for both cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive (99m)Tc homologs enables the use of identical molecules for therapy and imaging (theragnostic). The syntheses and in vitro evaluation of [(Cp-R)M(CO)(3)] (Cp=cyclopentadienyl, M=Re, (99m)Tc) with R being a highly potent carbonic-anhydrase-targeting vector is reported.

Organoruthenium and Organoosmium Complexes of 2‐Pyridinecarbothioamides Functionalized with a Sulfonamide Motif: Synthesis, Cytotoxicity and Biomolecule Interactions

“…Some of these compounds demonstrated nanomolar affinities for the pharmaceutically relevant isozymes h ‐CA IX and h ‐CA XII, much higher affinity than that of acetazolamide, which is a benchmark organic inhibitor for CAs. A co‐crystal structure of a Re complex with h ‐CA II showed that the deprotonated nitrogen of the sulfonamide group bound to the catalytically active Zn center, and the [CpRe(CO) 3 ] moiety took part in hydrophobic interactions with Phe131, Leu198, and Pro202 . Biological activity and structure–activity relationships (SARs) for metallocenes functionalized with the sulfonamide pharmacophore through triazole, triazole–ester, triazole–amide, amide and urea linkers have been reported.…”

“…Ac o-crystal structure of aR e complex with h-CA II showed that the deprotonated nitrogen of the sulfonamide group bound to the catalytically activeZ n center,a nd the [CpRe(CO) 3 ]m oiety took part in hydrophobic interactions with Phe131,L eu198,a nd Pro202. [22] Biological activity and structure-activity relationships (SARs) for metallocenes functionalized with the sulfonamide pharmacophore through triazole, triazole-ester,t riazole-amide, amide and urea linkers have been reported. These compounds showed moderate to good inhibitory activity in vitro and some examples demonstrated high selectivity for cancer-associated CA IX and CA XII compared to off-target CA Iand CA II.…”

The synthesis of biologically relevant conjugates of Re(CO)3 using pyridine-2-carboxyaldehyde

“…The discovery of isozymes of carbonic anhydrase that are overexpressed in certain tumors has also encouraged researchers to create new sulfonamide compounds with applications such as targeting by luminescence or γ-emission [33, 34]. The publication of the crystal structure of carbonic anhydrase with the metal complex, Cp R Re (CO) 3 (R = arylsulfonamide) bound to the zinc ion at the active site highlights the interest in this area [35, 36]. Although 4-aminofluorescein is not fluorescent, the parent fluorescein molecule finds heavy use in cellular imaging, and the development of Re(CO) 3 + based luminescent molecules has been a goal of many research groups [11–13].…”

Human carbonic anhydrase II as host protein for the creation of artificial metalloenzymes: the asymmetric transfer hydrogenation of imines

“…18 This was recently conrmed with an X-ray structure of an aryl-sulfonamide-bearing Ru pianostool complex incorporated within hCA II. 19,20 However, this latter proved catalytically inactive for a variety of transformations. Herein we report on our efforts to create an articial transfer hydrogenase based on the incorporation of a catalytically active iridium pianostool complex within hCA II, Fig.…”