Design and Synthesis of Acridine-Triazole and Acridine-Thiadiazole Derivatives and Their Inhibitory Effect against Cancer Cells

• DOI: 10.3390/ijms24010064
• Publication Date: 2022-12-21T08:31:06Z
• Authors: Lini Huo; Xiaochen Liu; Yogini Jaiswal; Hao Xu; Rui Chen; Rumei Lu; Yaqin Nong; Leonard Williams; Yan Liang; Zhiruo Jia
• Keywords: Acridine orange; Acridine

We report herein the design and synthesis of a series novel acridine-triazole acridine-thiadiazole derivatives. The newly synthesized compounds key intermediates were all evaluated for their antitumor activities against human foreskin fibroblasts (HFF), gastric cancer cells-803 (MGC-803), hepatocellular carcinoma bel-7404 (BEL-7404), large cell lung cells (NCI-H460), bladder (T24). Most exhibited high levels activity MGC-803 T24 but low toxicity normal liver (LO2), effect was even better than commercial anticancer drugs, 5-fluorouracil (5-FU) cis-platinum. Further, pharmacological mechanisms such as topo I, cycle, apoptosis, neovascularization evaluated. Only few potent I inhibitory at 100 μM. In addition, most active with an IC50 value 5.52–8.93 μM chosen, they could induce apoptosis in G2 stage or mainly arrest S stage. To our delight, lower zebrafish cytotoxicity strongly inhibit formation sub-intestinal veins, indicating potential clinical application.