2. Academic Validation
  3. Design, synthesis, and biological evaluation of β-carboline 1,3,4-oxadiazole based hybrids as HDAC inhibitors with potential antitumor effects

Design, synthesis, and biological evaluation of β-carboline 1,3,4-oxadiazole based hybrids as HDAC inhibitors with potential antitumor effects

  • Bioorg Med Chem Lett. 2022 May 15:64:128663. doi: 10.1016/j.bmcl.2022.128663.
Caizhi Tian 1,  Shuoqi Huang 2,  Zihua Xu 3,  Wenwu Liu 1,  Deping Li 4,  Mingyue Liu 2,  Chengze Zhu 5,  Limeng Wu 1,  Xiaowen Jiang 1,  Huaiwei Ding 6,  Qingchun Zhao 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, PR China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 2 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, PR China; School of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 3 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, PR China.
  • 4 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, PR China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 5 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 6 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: dinghuaiwei627@163.com.
  • 7 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, PR China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: zhaoqingchun1967@163.com.
PMID: 35272009 DOI: 10.1016/j.bmcl.2022.128663
Abstract

A series of novel β-carboline 1,3,4-oxadiazole based hybrids were designed, synthesized, and tested for cytotoxicity and HDAC inhibition. Among the target compounds, compound ZDLT-1 displayed high inhibitory activity for class I HDACs 1, 2, and 3, and potent anti-proliferative activity against HCT116 cells with an IC50 value of 0.173 ± 0.018 μM, it also exhibited better inhibitory activity with an IC50 value of 6 nM for HDAC6 than SAHA (IC50 = 15 nM). Furthermore, the pharmacological experiment of Hoechst staining, colony formation, cell Apoptosis assay, and wound healing scratch assay indicated that compound ZDLT-1 was a potent cytotoxic agent against HCT116 cells with cell Apoptosis induction. Further, in silico prediction of physicochemical properties, drug-likeness, and ADME parameters suggested that compound ZDLT-1 is a promising Anticancer agent. Taken together, the high potency cytotoxicity and class I HDACs inhibitory activity of compound ZDLT-1, which with the β-carboline 1,3,4-oxadiazole based hybrids as potent Anticancer agents could be nominated for further modification and optimization.

Keywords

1,3,4-Oxadiazole; Anticancer; HCT116 cells; HDAC; β-carboline.

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