2. Academic Validation
  3. Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors

Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors

  • Bioorg Med Chem. 2017 Jun 15;25(12):3116-3126. doi: 10.1016/j.bmc.2017.03.065.
Xiaoyan Han 1,  Yifan Zhong 1,  Guan Zhou 1,  Hui Qi 1,  Shengbin Li 1,  Qiang Ding 1,  Zhenming Liu 2,  Yali Song 3,  Xiaoqiang Qiao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China.
  • 2 Drug Design Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 3 Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China. Electronic address: yalisong@hbu.edu.cn.
  • 4 Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China; Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China. Electronic address: xiaoqiao@hbu.edu.cn.
PMID: 28462840 DOI: 10.1016/j.bmc.2017.03.065
Abstract

A new series of thirteen N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester compounds were synthesized and evaluated for antiproliferative activity against four different human Cancer cell lines: cervical Cancer (HeLa), lung Cancer (A549), gastric Cancer (MGC-803) and breast Cancer (MCF-7) as well as Topoisomerase I and IIα inhibitory activity. Compounds (5a, 5b, 5e, 8a, 8b) showed significant antiproliferative activity with low IC50 values against the four Cancer cell lines. Equally, compounds 5a, 5b, 5e, 5f, 8a, 8d, 8e and 8f showed Topoisomerase IIα inhibitory activity at 100μM with 5b, 5e, 8f exhibiting potential Topoisomerase IIα inhibitory activity compared to positive control at 100μM and 20μM, respectively. Conversely compounds 5e, 5f, 5g and 8a showed weaker Topoisomerase I inhibitory activity compared to positive control at 100μM. Compound 5b exhibited the most potent Topoisomerase IIα inhibitory activity at low concentration and better antiproliferative activity against the four human Cancer cell lines. The molecular interactions between compounds 5a-5g, 8a-8f and the Topoisomerase IIα (PDB ID: 1ZXM) were further investigated through molecular docking. The results indicated that these compounds could serve as promising leads for further optimization as novel antitumor agents.

Keywords

Anticancer activity; Molecular docking; N-(carbobenzyloxy) derivatives; Topoisomerase IIα inhibitor.

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