- New homocamptothecins: Synthesis, antitumor activity, and molecular modeling
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Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered β-hydroxylactone in place of the conventional six-membered α-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 9l, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity.
- Miao, Zhenyuan,Sheng, Chunquan,Zhang, Wannian,Ji, Haitao,Zhang, Jing,Shao, Luecheng,You, Liang,Zhang, Min,Yao, Jianzhong,Che, Xiaoyin
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p. 1493 - 1510
(2008/09/17)
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- Simple Synthesis of Indoles and of Corresponding 3(2H)-Indolone Derivatives, Monosubstituted at the Benzene Ring, as Synthetic Precursors of Natural Compounds
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Application of a specific BCl3-catalyzed ortho-chloroacetylation of the monosubstituted primary anilines 2a-e with chloroacetonitrile, as a variant of the Houben-Hoesch reaction, leads to the corresponding 2-amino-α-chloroacetophenones 3a-g.These may be reduced and cyclized to yield the indoles 4a-g or, after acylation to 5a-g and 7a, b converted by base-catalyzed dehydrochlorination into the 1-acyl-3(2H)-indolones 6a-g and 8a, b.
- Nimtz, Manfred,Haefelinger, Guenter
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p. 765 - 770
(2007/10/02)
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