当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 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.

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.

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 compound F10 arrested at G2/M phase, inhibited cell colony formatting and induced extrinsic and intrinsic apoptosis in MGC-803 and SGC-7901 cells. Collectively, compound F10 was the first to be reported as a new anticancer agent in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Song J,Gao QL,Wu BW,Zhu T,Cui XX,Jin CJ,Wang SY,Wang SH,Fu DJ,Liu HM,Zhang SY,Zhang YB,Li YC

doi

10.1016/j.ejmech.2020.112618

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

112618

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30590-0

journal_volume

203

pub_type

杂志文章

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