Ning Lei

Publications (3)6.78 Total impact

• Source

  Available from: Chunlin Zhuang

  Article: Synthesis and preliminary bioevaluation of novel E-ring modified acetal analog of camptothecin as cytotoxic agents.

  Lingjian Zhu, Chunlin Zhuang, Ning Lei, Zizhao Guo, Chunquan Sheng, Guoqiang Dong, Shengzheng Wang, Yongqiang Zhang, Jianzhong Yao, Zhenyuan Miao, Wannian Zhang
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  ABSTRACT: In an effort to improve the metabolic stability of the E-ring and decrease the toxicity of camptothecin (CPT), a novel cytotoxic acetal analog with 21-alkoxy groups was designed and synthesized. The preliminary results revealed that this class of compounds showed superior antiproliferative activity in vitro and moderate in vivo activity, while their topoisomerase I (Topo I) inhibitory activity was weakened significantly. The implications of these results within the current understanding of the structure-activity relationship of camptothecin are analyzed in detail. The obtained information provides insight into the role of the 21-carbonyl group in the binding of CPT to Topo I-DNA complex.
  European journal of medicinal chemistry 10/2012; 56:1-9. · 3.27 Impact Factor
• Article: Synthesis and biological evaluation of 7-alkenyl homocamptothecins as potent topoisomerase I inhibitors.

  Lingjian Zhu, Xianghua Zhang, Ning Lei, Wenfeng Liu, Zhenyuan Miao, Chunlin Zhuang, Chunquan Sheng, Wei Guo, Guoqiang Dong, Jianzhong Yao, Pengfei Cheng, Wannian Zhang
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  ABSTRACT: Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.
  Chemistry & Biodiversity 06/2012; 9(6):1084-94. · 1.80 Impact Factor
• Article: Synthesis and biological evaluation of novel homocamptothecins conjugating with dihydropyrimidine derivatives as potent topoisomerase I inhibitors.

  Lingjian Zhu, Pengfei Cheng, Ning Lei, Jianzhong Yao, Chunquan Sheng, Chunlin Zhuang, Wei Guo, Wenfeng Liu, Yongqiang Zhang, Guoqiang Dong, Shengzhang Wang, Zhenyuan Miao, Wannian Zhang
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  ABSTRACT: Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH₂) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7-formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435 and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.
  Archiv der Pharmazie 09/2011; 344(11):726-34. · 1.71 Impact Factor