Synthesis and biological evaluation of novel 2,3-dihydrochromeno[3,4-d]imidazol-4(1H)-one derivatives as potent anticancer cell proliferation and migration agents

• Published in: European journal of medicinal chemistry Vol. 114; pp. 232 - 243
• Main Authors: Han, Xuan, Luo, Jiang, Wu, Feng, Hou, XueYan, Yan, Guoyi, Zhou, Meng, Zhang, Mengqi, Pu, Chunlan, Li, Rui
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 23.05.2016; Elsevier
• Subjects: Animals; Anti-cancer agents; Anti-metastasis; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemistry, Medicinal; Chromeno [3,4-d] imidazol-4(1H)-one; Chromones - chemical synthesis; Chromones - chemistry; Chromones - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Life Sciences & Biomedicine; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Tumor Cells, Cultured; Anti-metastasis; Anti-cancer agents; Chromeno [3,4-d] imidazol-4(1H)-one; APOPTOSIS; CHROMATIN; BET RECRUITMENT; DOCKING; GROWTH; INHIBITOR; IDENTIFICATION; CANCER; COUMARIN DERIVATIVES
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.01.035

In this study, a series of novel molecules containing chromeno [3,4-d] imidazol-4(1H)-one was synthesized and their biological activities were evaluated. Among them, compound 35 showed a dramatic anticancer activity against HCT116 and MCF-7, and the flow cytometry assays demonstrated that it could arrest G0/G1 cell-cycle and induce apoptosis of SW620 cells in a dose-dependent manner. Besides, it also blocked MCF-7 cancer cell migration. Moreover, it inhibited tumor growth in HCT116 subcutaneously implanted xenografted mice. Taken together, compound 35 may be a promising candidate for anti-cancer agent as well as metastatic one. [Display omitted] •We have found a novel scaffold with better potency as antitumor agents.•Target compound 35 could arrest G0/G1 cell-cycle and induce apoptosis of SW620 cells in a dose-dependent manner.•35 blocked MCF-7 cancer cell migration with low toxicity to normal LO2 cells.•35 inhibited tumor growth by 52.96% at 80 mg/kg/48 h for 20 days.