2.B.24 The 2,6-Bis(benzimidazol-2-yl)pyridine/benzene Anion Carrier (BBP/B-AC) Family
2,6-Bis(benzimidazol-2-yl)pyridine exhibits potent anionophoric activity via processes of both Cl-/NO3- antiport and H+/Cl- symport. By contrast, its corresponding N-methylated analog exhibits negligible activity, revealing the importance of the imidazolyl-NH group in the anion-transport process (Peng et al. 2016).
A series of 1,3-bis(benzimidazol-2-yl)benzene (m-Bimbe) derivatives also exhibit excellent performance as transmembrane anion carriers with anticancer activity. The transport efficiency of m-Bimbe and its derivatives was optimized by adding a strong electron-withdrawing nitro group at the 5-position of the central phenyl subunits to enhance CH-anion interactions (Yu et al. 2018). The 5-nitrated derivatives having nitro or trifluoromethyl groups at the benzimidazoloyl rings exhibit 2400- and 1700-fold enhanced anionophoric activity with EC50 values as low as 36 and 50nM, respectively. These compounds disturb cellular homeostasis of chloride anions, modify the intracellular pH and induce the basification of acidic organelles. Most of this series of m-Bimbe derivatives exhibit cytotoxicity toward tested human solid tumor cell lines, and the 5-nitrated derivative bearing trifluoromethyl groups at the benzimidazoloyl ring is the most active with an IC50 value in the low micromolar range (Yu et al. 2018).