Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
Org Biomol Chem. 2019 Feb 6;17(6):1558-1571. doi: 10.1039/c8ob03036g.
Anion transporters have attracted substantial interest due to their ability to induce cell apoptosis by disrupting cellular anion homeostasis. In this paper we describe the synthesis, anion recognition, transmembrane anion transport and cell apoptosis-inducing activity of a series of fluorinated 1,3-bis(benzimidazol-2-yl)benzene derivatives. These compounds were synthesized from the condensation of 1,3-benzenedialdehyde or 5-fluoro-1,3-benzenedialdehyde with the corresponding 1,2-benzenediamines and fully characterized. They are able to form stable complexes with chloride anions, and exhibit potent liposomal and in vitro anionophoric activity. Their anion transport efficiency may be ameliorated by the total number of fluorine atoms, and the enhanced anionophoric activity was a likely consequence of the increased lipophilicity induced by fluorination. Most of these fluorinated bisbenzimidazoles exhibit potent cytotoxicity toward the selected cancer cells. Mechanistic investigations suggest that these compounds are able to trigger cell apoptosis probably by disrupting the homeostasis of chloride anions.
阴离子转运体由于能够通过破坏细胞阴离子稳态诱导细胞凋亡而引起了广泛的关注。在本文中，我们描述了一系列氟化 1,3-双（苯并咪唑-2-基）苯衍生物的合成、阴离子识别、跨膜阴离子转运和诱导细胞凋亡活性。这些化合物是通过 1,3-苯二甲醛或 5-氟-1,3-苯二甲醛与相应的 1,2-苯二胺缩合而成，并进行了充分的表征。它们能够与氯离子形成稳定的配合物，并表现出有效的脂质体和体外阴离子载体活性。它们的阴离子转运效率可以通过氟原子的总数来改善，而阴离子载体活性的增强可能是由于氟化引起的亲脂性增加所致。这些氟化双苯并咪唑中有许多对选定的癌细胞表现出很强的细胞毒性。机制研究表明，这些化合物能够通过破坏氯离子的稳态来触发细胞凋亡。
