Thieno[2,3-b]pyridines—A new class of multidrug resistance (MDR) modulators

Abstract

To identify new potent multidrug resistance modulators, we have synthesized a series of novel thieno[2,3-b]pyridines and furo[2,3-b]pyridines, and examined their stucture–activity relationships. All synthesized compounds were tested to determine BCRP1, P-gp, and MRP1 inhibitor activity, and most potent MDR modulators were also screened for their toxicity, cytotoxicity and Ca2+ channel antagonist activity. Among these compounds, thieno[2,3-b]pyridine (6r) was found to exhibit a potent P-gp inhibitory action with EC50=0.3±0.2μM, MRP1 inhibitory action with EC50=1.1±0.1μM and BCRP1 inhibitory action with EC50=0.2±0.05μM and may represent suitable candidate for further pharmacological studies.