Synthesis and biological evaluation of 2′,5′-dimethoxychalcone derivatives as microtubule-targeted anticancer agents
Journal
Bioorganic and Medicinal Chemistry
Journal Volume
18
Journal Issue
6
Pages
2089-2098
Date Issued
2010
Author(s)
Abstract
A series of novel 2′,5′-dimethoxylchalcone derivatives including 18 new compounds were synthesized and evaluated for cytotoxicities against two human cancer cell lines, NTUB1 (human bladder cancer cell line) and PC3 (human prostate cancer cell line). All these derivatives except for 21 exhibited significant cytotoxic effect against NTUB1 and PC3 cell lines. Compounds 13 and 17 with 4-carbamoyl moiety showed potent inhibitory effect on growth of NTUB1 and PC3 cells. Flow cytometric analysis demonstrated that treatment of NTUB1 cells with 1 μM 13 and 17 induced G1 phase arrest accompanied by an increase in apoptotic cell death of NTUB1 cells after 24 h. Treatment of PC3 cells with 1 μM and 3 μM 13, and 1 μM and 3 μM 17 induced S and G1, and G1 and G2/M phase arrests, respectively, accompanied by an increase in apoptotic cell death. These data suggested that 13 and 17 with different 4-carbamoyl moiety displayed same cell cycle arrest in NTUB1 cells while different doses of 13 and 17 revealed different cell cycle arrest in PC3 cells. Cell morphological study of 17 indicated that more cells rounding up or dead associated with tubulin polymerization. Compound 17 showed an increased α-tubulin level in polymerized microtubule fraction in a dose-dependent manner while 500 nM paclitaxel also showed similar effect in NTUB1 cells by Western blot analysis. The result suggested that 17 may be used as microtubule-targeted agents. ? 2010 Elsevier Ltd. All rights reserved.
Subjects
Anti-mitotic; Anticancer; Chalcone; Claisen-Schmidt condensation; Microtubule; Paclitaxel; Synthesis; Tubulin polymerization
SDGs
Other Subjects
2',5' dimethoxychalcone derivative; 4 (2 methylethyl)carbamoyl 2',5' dimethoxychalcone; 4 tetrahydropyrrolylcarbamoyl 2',5' dimethoxychalcone; antineoplastic agent; chalcone derivative; cisplatin; unclassified drug; antineoplastic activity; article; cancer cell culture; cancer inhibition; cell cycle regulation; controlled study; drug synthesis; drug targeting; human; human cell; microtubule; reaction analysis; Antineoplastic Agents; Cell Cycle; Cell Proliferation; Cell Survival; Chalcones; Drug Screening Assays, Antitumor; Humans; Microtubules; Structure-Activity Relationship; Tumor Cells, Cultured
Type
journal article