Hong Xiao-Qiao, He Xiang-Yu, Tam Kin Yip, Chen Wen-Hua
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau, PR China.
Bioorg Med Chem Lett. 2020 Oct 1;30(19):127461. doi: 10.1016/j.bmcl.2020.127461. Epub 2020 Aug 2.
Two lysosome-targeting fluorescent anion transporters derived from coumarins, trifluoromethylated arylsquaramides and morpholines were synthesized, and their specificity and efficiency to target and alkalize lysosomes were investigated. They are able to target lysosomes specifically. Compared with the previous analogue without trifluoromethyl substituents, these two conjugates, in particular the one having a 3,5-bis(trifluoromethyl) substituent, exhibit significantly higher ability to facilitate the transport of chloride anions, alkalize lysosomes and reduce the activity of lysosomal Cathepsin B enzyme. The present finding suggests that improving the anionophoric activity of lysosome-targeting fluorescent anion transporters is favorable to the efficiency to alkalize lysosomes and deactivate lysosomal Cathepsin B enzyme.
合成了两种源自香豆素、三氟甲基化芳基方酸二酰胺和吗啉的靶向溶酶体的荧光阴离子转运体，并研究了它们靶向和碱化溶酶体的特异性和效率。它们能够特异性地靶向溶酶体。与先前没有三氟甲基取代基的类似物相比，这两种缀合物，特别是具有3,5-双（三氟甲基）取代基的缀合物，在促进氯离子转运、碱化溶酶体和降低溶酶体组织蛋白酶B酶活性方面表现出显著更高的能力。目前的发现表明，提高靶向溶酶体的荧光阴离子转运体的阴离子载体活性有利于碱化溶酶体和使溶酶体组织蛋白酶B酶失活的效率。
