2. Academic Validation
  3. Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors

Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors

  • Bioorg Med Chem Lett. 2020 Jan 15;30(2):126816. doi: 10.1016/j.bmcl.2019.126816.
Peng-Cheng Diao 1,  Xie-Er Jian 1,  Peng Chen 1,  Chuan Huang 1,  Jie Yin 1,  Jie Chun Huang 1,  Jun-Sheng Li 1,  Pei-Liang Zhao 2
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
  • 2 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
PMID: 31753698 DOI: 10.1016/j.bmcl.2019.126816
Abstract

A series of novel indole-based oxalamide and aminoacetamide derivatives were designed, synthesized, and evaluated for antiproliferative activities. Preliminary results revealed that compound 8g exhibited significant antiproliferative effect against PC-3, HeLa and HCT-116 cell lines. Flow cytometric analysis of the cell cycle demonstrated the compound 8g induced the cell cycle arrest at G2/M phase in HeLa cell lines. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 8g andinhibition of tubulinpolymerization. Additionally, molecular docking analysis suggested that 8g formed stable interactions in the colchicine-binding site of tubulin. These preliminary results demonstrated that a new class of novel indole-based oxalamide and aminoacetamide derivatives described in the investigation could be developed as potential scaffolds to new Anticancer agents.

Keywords

Antiproliferative activity; Indoles; Synthesis; Tubulin polymerization.

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