Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases

Abstract

Human carbonic anhydrases IX and XII are upregulated in many tumors and form a novel target for new generation anticancer drugs. Here we report the synthesis of novel 2-indolinone derivatives with the sulfonamide group as a zinc binding moiety. Enzyme inhibition assays confirmed that the compounds showed selectivity against hCA IX and XII over the widely distributed off-targets hCA I and II. Molecular modelling studies were performed to suggest modes of binding for these compounds. (C) 2017 Elsevier Ltd. All rights reserved.