2. Academic Validation
  3. Design, synthesis and evaluation of 4-substituted anthra[2,1-c][1,2,5]thiadiazole-6,11-dione derivatives as novel non-camptothecin topoisomerase I inhibitors

Design, synthesis and evaluation of 4-substituted anthra[2,1-c][1,2,5]thiadiazole-6,11-dione derivatives as novel non-camptothecin topoisomerase I inhibitors

  • Bioorg Med Chem Lett. 2017 May 1;27(9):1929-1933. doi: 10.1016/j.bmcl.2017.03.039.
Guoqiang Dong 1,  Yuxin Fang 1,  Yang Liu 2,  Na Liu 1,  Shanchao Wu 1,  Wannian Zhang 1,  Chunquan Sheng 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 2 Department of Pharmacy, No. 401 Hospital of Chinese People's Liberation Army, Qingdao 266071, People's Republic of China.
  • 3 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: shengcq@hotmail.com.
PMID: 28351590 DOI: 10.1016/j.bmcl.2017.03.039
Abstract

Previously, 4-tosylanthra[1,2-c][1,2,5]thiadiazole-6,11-dione (1) was identified as a novel non-camptothecin Topoisomerase I (Top1) inhibitor by structure-based virtual screening. Herein, a series of 4-substituted derivatives were designed and synthesized. Most of them showed potent Top1 inhibitory activity. Their in vitro antiproliferative activity was also evaluated in A549, HCT-116 and ZR-75-30 human Cancer cell lines. Compound 8s showed good antiproliferative activity with IC50 of 0.52μM and 0.42μM against HCT-116 and ZR-75-30 cell line, respectively. Top1 unwinding assay and molecular modeling studies rationalized the mode of action of this new class of inhibitors.

Keywords

Anthrathiadiazole; Antiproliferative activity; Structure-activity relationship; Topoisomerase I inhibitors.

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