Structure-based hybridization, synthesis and biological evaluation of novel tetracyclic heterocyclic azathioxanthone analogues as potential antitumor agents

  • Eur J Med Chem. 2015 Oct 20:103:615-27. doi: 10.1016/j.ejmech.2014.09.050.
Tsung-Chih Chen  1 ,  Chia-Lun Wu  2 ,  Chia-Chung Lee  1 ,  Chun-Liang Chen  1 ,  Dah-Shyong Yu  3 ,  Hsu-Shan Huang  4
Affiliations
  • 1. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
  • 2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
  • 3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital, Taipei 114, Taiwan. Electronic address: [email protected].
  • 4. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: [email protected].
PMID: 25799376 DOI: 10.1016/j.ejmech.2014.09.050
Abstract

A series of tetracyclic heterocyclic azathioxanthones were synthesized and evaluated for cell proliferations, Topoisomerase inhibitions, and NCI-60 cell panel assay, respectively. Compounds 5, 7, 8, 16, and 19 were selected for Topoisomerase assay after MTT assay. 7 not only showed cytotoxic effect (IC50 = 2.84 ± 0.64 μM) in PC-3 cells but also revealed topoisomerases inhibition with IC50 (10-25 μM) and increased apoptotic cleavage of PARP and Caspase 3 activity. The overall of novel azathioxanthones with different cytostatic and cytotoxic activities should be further developed as new potential candidates for Anticancer drugs.

Keywords
Azathioxanthones; Cytostatic and cytotoxic activities; MTT assay; NCI-60 human tumor cell lines; Topoisomerase assays.