Synthesis and biological activity of 5-sulfonamide-substituted 3-hydroxyoxindoles with 3-cyanomethyl and 3-carboxymethyl groups

Abstract

It was shown that sulfochlorination of isatins followed by reaction with amines and then with malonic acid derivatives is an efficient and highly efficient method for the synthesis of substituted oxindoles. The synthesis of a series of new 3-cyanomethyl- and 3-carboxymethyl-3-hydroxy-2-oxoindoline-5-sulfonamides was carried out, and their biological activity was evaluated in vitro for their effects on mitochondrial functions, lipid peroxidation, and the activity of recombinant human carbonic anhydrase II. It was found that the new compounds have weak antioxidant activity, do not affect mitochondrial membrane potential, and have low cytotoxicity towards human neuroblastoma SH-SY5Y cells. The effect of these compounds on intraocular pressure (IOP) was tested in experiments in vivo. A lead compound was identified that inhibited carbonic anhydrase II esterase activity with 99% efficiency at a concentration of 10 µmol L⁻¹, but no correlation was observed between inhibition of carbonic anhydrase II and IOP reduction. At the same time, compounds effectively reducing IOP in rabbits and rats were found. Simultaneously, it was shown that the antiglaucomatous effect of the compounds varies depending on the animal species.