Design, synthesis and anti-cancer evaluation of genistein-1, 3, 5-triazine derivatives. (21st March 2023)

• Record Type: Journal Article
• Authors: Zou, Jing-Pei; Zhang, Zhen; Lv, Jin-Yu; Zhang, Xiao-Qing; Zhang, Zhao-Yuan; Han, Shu-Tong; Liu, Yu-Wei; Liu, Wei-Wei; Ji, Jing; Shi, Da-Hua
• Is Part Of: Tetrahedron. Volume 134(2023)
• Publication Date: 2023-03-21
• Subjects: Genistein -- 1, 3, 5-Triazine -- Anti-cancer -- Antiproliferative activities; TWTYHMFTVNITCD-UHFFFAOYSA-N -- XMBJOBAMRLIAGK-UHFFFAOYSA-N -- GHVRFQJEARMJMC-UHFFFAOYSA-N -- IVXQRWSGYDWJRP-UHFFFAOYSA-N -- OKCSICOMRUGNIS-UHFFFAOYSA-N -- LJIGAAGQQVROCO-UHFFFAOYSA-N -- YQNZRICCKZUACG-UHFFFAOYSA-N -- MTBIMIBWWOLCIH-UHFFFAOYSA-N -- TUBCJOLKQOHBJF-UHFFFAOYSA-N -- MTRUGHMEPVVHCQ-UHFFFAOYSA-N -- GZOIYESWLUBRJU-UHFFFAOYSA-N -- LRXISSFPLRINBL-UHFFFAOYSA-N; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2023.133293
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Twelve genistein-1, 3, 5-triazine derivatives were synthesized by nucleophilic substitution and characterized by 1 H NMR, 13 C NMR, IR, HR-MS and single crystal X-ray diffraction. The purity of target compounds was determined to be above 99% by HPLC. Antiproliferative activities of these compounds against MDA-MB-231 (breast), HeLa (cervical), HCT-116 (prostate) and Huh-7 (liver) cancer cell lines were evaluated by the MTT assay. Most genistein-1, 3, 5-triazine derivatives showed better anti-cancer activity than nuclear parent genistein. Compound 4i displayed the strongest antiproliferative activity against MDA-MB-231 cells (IC50 = 23.13 μM), which was better than 5-fluorouracil (IC50 = 78.04 μM). Further studies showed that compound 4i not only could inhibit the migration, invasion and adhesion of MDA-MB-231 cells, but also had great inhibitory effects on the proliferation of MDA-MB-231 tumor xenografts in vivo . In addition, ADME properties and toxicity prediction showed that these compounds may possess the properties to be drug candidates. Thus, compound 4i may be a promising lead compound for the treatment of breast cancer. Graphical abstract: Image 1 Highlight: Design and synthesis of twelve genistein-1, 3, 5-triazine derivatives. Compound 4i displayed the strongest antiproliferative activity against MDA-MB-231 cells than the standard 5-fluorouracil. Compound 4i could inhibit the migration, invasion and adhesion of MDA-MB-231 cells. Compound 4i showed great inhibitory effects on the proliferation of MDA-MB-231 tumor xenografts in vivo.