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

Abstract

Anticancer‐active RuII–η6‐p‐cymene complexes of bioactive 2‐pyridinecarbothioamide ligands have been shown to have high selectivity for plectin and can be administered orally. Reported herein is the functionalization of a 2‐pyridinecarbothioamide with a sulfonamide group and its conversion into M–η6‐p‐cymene complexes (M = Ru, Os). The presence of a sulfonamide moiety in many organic drugs and metal complexes endows these agents with interesting biological properties and can transform the latter into multi‐targeted agents. The compounds were characterized with standard methods and the in vitro anticancer activity data was compared with studies on the hydrolytic stability of the complexes and their reactivity to small biomolecules. A molecular modeling study revealed plausible modes of binding of the complexes in the catalytic pocket of carbonic anhydrase II.

Impact of the Metal Center and Leaving Group on the Anticancer Activity of Organometallic Complexes of Pyridine-2-carbothioamide

“…The spectra featured peaks at m/z values assignable to the [M − X] + ions while the base peak was attributed to the [M − 2X − H] + ions. A similar ionization behavior in ESI-MS was observed for other PCA-metal complexes [34,35,37,38]. The experimental m/z values as well as the isotopic distribution pattern closely resembled the calculated values.…”

Effect of an Imidazole-Containing Schiff Base of an Aromatic Sulfonamide on the Cytotoxic Efficacy of N,N-Coordinated Half-Sandwich Ruthenium(II) p-Cymene Complexes

“…Acetazolamide, methazolamide, ethoxzolamide, saccharin, brinzolamide, and dorzolamide molecules inhibit CAs. , Among the various isoforms of CAs, it is now thought that CA IX and CA XII are two membrane-bound isoforms that help to control the pH of cancer cells in a hypoxic environment. Thus, hypoxia-inducible CA IX appears to be a promising target for anticancer therapy because of its overexpression in many cancer cells compared to normal cells. − The activity of CA targeting sulfonamides may be modified and improved upon binding to transition-metal ions. ,− It was recently shown that 4-(2-aminoethyl)­benzenesulfonamide (AEBS)-bound gold nanoparticles selectivity target CA IX over CA I and CA II . Hence, sulfonamides have the scope to target cancer cells over normal cells selectively.…”

Organometallic anti-tumor agents: targeting from biomolecules to dynamic bioprocesses

“…105 Therefore, benzene sulfonamides are a wellknown class of CA inhibitors and have been recently applied for targeted anti-tumor metallodrug construction. [106][107][108][109][110][111] For instance, our group developed rhenium(I) tricarbonyl complex 2-60 that is functionalized with a terthiophene group for photodynamic therapy (PDT) and a benzene sulfonamide for CA IX inhibition (Fig. 16(a)).…”