2. Academic Validation
  3. Design, synthesis and evaluation of novel sophoridinic imine derivatives containing conjugated planar structure as potent anticancer agents

Design, synthesis and evaluation of novel sophoridinic imine derivatives containing conjugated planar structure as potent anticancer agents

  • Bioorg Med Chem. 2018 Aug 7;26(14):4136-4144. doi: 10.1016/j.bmc.2018.07.001.
Yiming Xu 1,  Dewang Jing 1,  Rui Chen 2,  Haroon Ur Rashid 3,  Jun Jiang 1,  Xu Liu 4,  Lisheng Wang 5,  Peng Xie 6
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
  • 2 Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning 530004, China.
  • 3 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China; Department of Chemistry, Sarhad University of Science & Information Technology, Peshawar, Khyber Pakhtunkhwa 25120, Pakistan.
  • 4 Medicinal College, Guangxi University, Nanning 530004, China.
  • 5 Medicinal College, Guangxi University, Nanning 530004, China. Electronic address: lswang@gxu.edu.cn.
  • 6 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. Electronic address: xiep@gxu.edu.cn.
PMID: 30007563 DOI: 10.1016/j.bmc.2018.07.001
Abstract

Based on our previous study and the binding mode of camptothecin with Topo I, a series of novel sophoridine imine derivatives containing conjugated planar structure were designed, synthesized and tested for their in vitro Anticancer activity. The results showed that most of the derivatives displayed potent activity. In particular, compounds 10b exhibited excellent anti-proliferative activities with IC50 5.7 µM and 8.5 µM against HepG-2 and HeLa cell lines, respectively. Molecular docking studies revealed that the introduction of conjugated planar structure could form π-π stacking interaction with DNA, leading to the improvement of biological activity. Its mode of action was to inhibit the activity of DNA Topo I, followed by the G0/G1 phase arrest. This work provides a theoretical basis for structural optimizations and exploring Anticancer pathways of this kind of compound and 10b could emerge as promising lead compounds for the development of novel Topo I inhibitors.

Keywords

Antitumor activity; Camptothecin; Schiff base; Sophoridine; Topoisomerase I.

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