Discovery of tertiary amide derivatives incorporating benzothiazole moiety as anti-gastric cancer agents in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway.

European Journal of Medicinal Chemistry
Jian SongYong-Chun Li

Abstract

On the basis and continuation of our previous studies on anti-tubulin and anti-gastric cancer agents, novel tertiary amide derivatives incorporating benzothiazole moiety were synthesized and the antiproliferative activity was studied in vitro. Preliminary structure activity relationships (SARs) were explored according to the in vitro antiproliferative activity results. Some of compounds could significantly inhibit the proliferation of three cancer cells (HCT-116, MGC-803 and PC-3 cells) and compound F10 exhibited excellent antiproliferative activity against HCT-116 cells (IC50 = 0.182 μM), MGC-803 cells (IC50 = 0.035 μM), PC-3 cells(IC50 = 2.11 μM) and SGC-7901 cells (IC50 = 0.049 μM). Compound F10 effectively inhibited tubulin polymerization (IC50 = 1.9 μM) and bound to colchicine binding site of tubulin. Molecular docking results suggested compound F10 could bind tightly into the colchicine binding site of β-tubulin. Moreover, compound F10 could regulate the Hippo/YAP signaling pathway. Compound F10 activated Hippo signaling pathway from its very beginning MST1/2, as the result of Hippo cascade activation YAP were inhibited. And then it led to a decrease of c-Myc and Bcl-2 expression. Further molecular experiments showed that...Continue Reading

Citations

Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chao-Fan LuSai-Yang Zhang
Jan 21, 2021·Bioorganic & Medicinal Chemistry Letters·Ting ZhuSai-Yang Zhang
Apr 18, 2021·Journal of Cancer Research and Clinical Oncology·Hong-Li LiSai-Yang Zhang
May 10, 2021·Bioorganic & Medicinal Chemistry Letters·Shu-Yu WangTao Hu
May 23, 2021·Bioorganic & Medicinal Chemistry Letters·Shu-Yu WangTao Hu
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yong-Feng GuanSai-Yang Zhang
Sep 2, 2021·Archiv der Pharmazie·Kashif HaiderMohammad S Yar
Aug 30, 2021·European Journal of Medicinal Chemistry·Jian SongSai-Yang Zhang
Sep 30, 2021·Chemical Biology & Drug Design·Ramsha IftikharFaiza Rao

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