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Lan, Hairong; Song, Junying; Yuan, Juan; Xing, Aiping; Zeng, Dai; Hao, Yating; Zhang, Zhenqiang; Feng, Shuying
Molecules (Basel, Switzerland), 12/2022, Letnik: 28, Številka: 1Journal Article
In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds and were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC = 6.70 μM and 7.66 μM), respectively. Compounds and exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds and could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that and bind with DNA via groove binding and partial intercalation. These results demonstrated that and may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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