Pegylation approach applied to erlotinib–carbonic anhydrase inhibitors hybrids towards anticancer agents†

Abstract

Herein we report a first study on single molecular entities bearing both epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA) inhibiting moieties as new tools for the management of hypoxic cancers. Specifically, we designed and synthesized a library of erlotinib (ERL)-based compounds bearing both the primary sulfonamide/coumarin moieties with the intent to selectively interfere with EGFR and CA targets respectively. The compounds obtained were investigated in silico and in vitro for their ability to interact with the appropriate targets followed by the assessment on selected compounds for the anti-proliferative activity using human (h) TNBC cell line MDA-MB-231. We are confident that the data provided in this study are fundamental for paving the way toward the development of multi-targeting molecular structures useful for the management of chronic diseases such as hypoxic tumors.