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Volume 10
Journal of Cancer Science & Therapy
Oncologists 2018
May 24-25, 2018
May 24-25, 2018 Osaka, Japan
22
nd
Global Annual Oncologists Meeting
J Cancer Sci Ther 2018, Volume 10
DOI: 10.4172/1948-5956-C3-130
Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37
interaction disruptors that inhibit cell migration and reverse drug resistance
Le Jin and Min Ji
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 micro-molar 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.
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