biostudies-literatureWei YShandong ProvinceShenzhen Science and Technology Innovation CommitteeMinistry of Science and Technology of the People's Republic of ChinaMinistry of Education of the People's Republic of ChinaScience and Technology Department of TibetNational Natural Science Foundation of ChinaWuhan Municipal Bureau of Science and TechnologyKey Research Project of YantaiScience and Technology Support Program for Youth Innovation in Universities of ShandongHubei Province9196-9203https://www.ebi.ac.uk/biostudies/studies/S-EPMC8028158biostudies-literatureUnknown6(13)Transient receptor potential canonical channel 6 (TRPC6) has been implicated in many kinds of malignant tumors, but very few potent TRPC6 antagonists are available. In this study, a benzothiazole amide derivative 1a was discovered as a TRPC6 activator in a cell-based high-throughput screening. A series of benzothiazole amide derivatives were designed and synthesized. The docking analyses indicated that the conformations of the compounds bound to TRPC6 determined the agonistic or antagonistic activity of the compounds against TRPC6, and compound 1s with the tetrahydronaphthalene group in R1 position fit well into the binding pocket of the antagonist-bound conformation of TRPC6. Compound 1s showed an inhibitory potency order of TRPC3 (IC50 3.3 ± 0.13 μM) ≈ C6 (IC50 4.2 ± 0.1 μM) > C7 with good anti-gastric cancer activity in a micromolecular range against AGS and MKN-45, respectively. In addition, 1s inhibited the invasion and migration of MKN-45 cells in vitro.ACS omegaBenzothiazole Amides as TRPC3/6 Inhibitors for Gastric Cancer Treatment.PMC80281582020YFA0908800ZNJC201931817736742019XDHZ102JCYJ20190808152019182820738882020BAB0582019KJM009XZ202001YD0028C2019020701011429Yang GLyu ZLi FZhang MZeng XXu FWang HWei YDing MLiu YWang PHong XCao ZLu JTian TfalseBenzothiazole Amides as TRPC3/6 Inhibitors for Gastric Cancer Treatment.Transient receptor potential canonical channel 6 (TRPC6) has been implicated in many kinds of malignant tumors, but very few potent TRPC6 antagonists are available. In this study, a benzothiazole amide derivative 1a was discovered as a TRPC6 activator in a cell-based high-throughput screening. A series of benzothiazole amide derivatives were designed and synthesized. The docking analyses indicated that the conformations of the compounds bound to TRPC6 determined the agonistic or antagonistic activity of the compounds against TRPC6, and compound 1s with the tetrahydronaphthalene group in R1 position fit well into the binding pocket of the antagonist-bound conformation of TRPC6. Compound 1s showed an inhibitory potency order of TRPC3 (IC50 3.3 ± 0.13 μM) ≈ C6 (IC50 4.2 ± 0.1 μM) > C7 with good anti-gastric cancer activity in a micromolecular range against AGS and MKN-45, respectively. In addition, 1s inhibited the invasion and migration of MKN-45 cells in vitro.2021-01-01T00:00:00Z2021 Apr2026-05-03T19:56:23.156Z2022-02-09T14:45:37.6ZS-EPMC80281583384278810.1021/acsomega.1c00514