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Volume 9
Chemical Sciences Journal
Asia Chemistry 2018
September 12-13, 2018
11
th
Annual Congress on
September 12-13, 2018 Singapore
Chemistry
Discovery of 18β-Glycyrrhetinic acid Conjugated Aminobenzothiazole derivatives as Hsp90-Cdc37
interaction disruptors that inhibit Cell migration and Reverse Drug resistance
Le Jin
Southeast University, China
A series of 18β-Glycyrrhetinic Acid (GA) conjugated Aminobenzothiazole derivatives were designed, synthesized and evaluated
for disruption activity of Hsp90-Cdc37 as well as the effects of
in vitro
cell migration. These compounds exhibited relatively
good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active
compound 11 g revealed key interactions between 11 g and Hsp90-Cdc37 complex in which the Benzothiazole moiety and the
amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that
some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression
activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the
A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with
compound 11 g resulted in inhibition of
in vitro
cell migration through wound healing assay and S phase of cell cycle arrested.
In addition, 11 g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole
derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant.
745262415@qq.comChem Sci J 2018, Volume 9
DOI: 10.4172/2150-3494-C5-030