Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia

Li, Yang; Sun, Ying; Zhou, Yang; Li, Xinyang; Zhang, Huan; Zhang, Guojun

doi:10.1080/14756366.2020.1852556

Cited by 11 publications

(14 citation statements)

References 35 publications

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“…In fact, chalcone compounds have shown good therapeutic effects and clinical application potential as anticancer drugs for the treatment of human cancers [5][6][7]. In addition, chalcone fragment was also frequently utilized to design novel agents with other anticancer moieties to enhance the biological efficacy by the molecular hybridization strategy [8][9][10][11][12][13][14][15]. 4-Aminochalcone derivative 1 [12] displayed excellent inhibitory activity against NCI-H460, A549, and H1975 cells with IC 50 values of 2.3, 3.2, and 5.7 µM, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Molecules 2021, 26, x FOR PEER REVIEW 2 of 13 2 [13] was reported as a LSD1 inhibitor with an IC50 value of 0.14 µM. Compound 2 exhibited potent anticancer activity against MOLT-4 cells (IC50 = 0.87 µM) and was significantly effective in suppressing the growth of MOLT-4 xenograft tumor mouse model.…”

Section: Introductionmentioning

confidence: 99%

“…) 13. C NMR (100 MHz, DMSO-d 6 ) δ 187.52, 159.42, 149.29, 147.00, 146.09, 143.55, 140.90, 132.64, 131.52, 130.93, 130.01, 129.96, 129.26, 129.08, 124.85, 122.68, 121.47, 119.93, 119.06, 106.02, 25.60, 21.55.…”

mentioning

confidence: 99%

“…) 13. C NMR (100 MHz, DMSO-d 6 ) δ 187.46, 159.42, 149.38, 146.23, 144.70, 138.42, 131.92, 130.65, 129.96, 129.05, 128.04, 124.84, 122.69, 119.90, 119.56, 119.24, 119.17, 113.09, 110.95, 105.81, 55.95, 25.57.…”

mentioning

confidence: 99%

“…) 13. C NMR (100 MHz, DMSO-d 6 ) δ 193.40, 160.16, 159.44, 143.53, 137.15, 137.08, 131.12, 131.06, 130.37, 130.04, 129.86, 128.97, 128.70, 124.94, 122.68, 122.03, 119.97, 119.08, 118.93, 114.81, 114.69, 113.64, 55.42, 25.49.…”

mentioning

confidence: 99%

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Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives

et al. 2021

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The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound 12e exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC50 values of 1.38, 5.34, and 5.21 µM, respectively. The structure–activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound 12e inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound 12e could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound 12e might be a valuable lead compound for the development of anticancer agents.

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