title: Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives as potential antitumor candidate.
abstract: A novel class of tetrahydroisoquinoline derivatives was designed and synthesized as antitumor agents and evaluated for their in vitro and in vivo biological activities. The antiproliferative activities of all the target compounds on HUVEC, MCF-7, and HT-29 were evaluated. Compared with colchicine (1.04 × 10-2μm), 17d and 17e exhibited outstanding activity on MCF-7 with IC50values 0.26 × 10-2μm and 0.89 × 10-3μm in cell cytotoxicity assay. The tubulin polymerization assay demonstrated that 17d and 17e exhibited better inhibition rate. In the MCF-7-xenograft mouse model that was treated with 17d and 17e by intraperitoneal injection, the tumor weight was decreased at same rate with tamoxifen, and relative tumor proliferation rates were 59.48% and 41.33%, while tamoxifen was 45.08% with a daily dose of 20 mg/kg, which were demonstrated potent in vivo efficacy.
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Panhu
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Mohan
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Huicai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, Hefei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D019073:HT29 Cells / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D011034:Podophyllotoxin / Q000737:chemistry; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D044005:Tetrahydroisoquinolines; D014404:Tubulin; D050257:Tubulin Modulators; D011034:Podophyllotoxin
keywords: MCF-7; antitumor; selectivity; tetrahydroisoquinoline derivatives