Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents.

Article Details

Citation

Copy to clipboard

Yang W, Hu Y, Yang YS, Zhang F, Zhang YB, Wang XL, Tang JF, Zhong WQ, Zhu HL

Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents.

Bioorg Med Chem. 2013 Mar 1;21(5):1050-63. doi: 10.1016/j.bmc.2013.01.013. Epub 2013 Jan 16.

PubMed ID

23391364 [ View in PubMed

]

Abstract

Two series of novel naphthalin-containing pyrazoline derivatives C1-C14 and D1-D14 have been synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. Compound D14 displayed the most potent activity against EGFR and A549 cell line (IC(50)=0.05 muM and GI(50)=0.11 muM), being comparable with the positive control Erlotinib (IC(50)=0.03 muM and GI(50)=0.03 muM) and more potent than our previous compounds C0-A (IC(50)=5.31 muM and GI(50)=33.47 muM) and C0-B (IC(50)=0.09 muM and GI(50)=0.34 muM). Meanwhile, compound C14 displayed the most potent activity against HER-2 and MCF-7 cell line (IC(50)=0.88 muM and GI(50)=0.35 muM), being a little less potent than Erlotinib (IC(50)=0.16 muM and GI(50)=0.08 muM) but far more potent than C0-A (IC(50)=6.58 muM and GI(50)=27.62 muM) and C0-B (IC(50)=2.77 muM and GI(50)=3.79 muM). The docking simulation was performed to analyze the probable binding models and the QSAR models were built for reasonable design of EGFR/HER-2 inhibitors at present and in future. The structural modification of introducing naphthalin moiety reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. Moreover, the replacement of thiourea skeleton by using benzene ring resulted in the slight diversity of the two series towards specific targets.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erlotinib	Epidermal growth factor receptor	IC 50 (nM)	30	N/A	N/A	Details