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Updated: Feb 23, 2026

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS
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Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

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Developing antineoplastic agents that target peroxisomal enzymes: cytisine-linked isoflavonoids as inhibitors of

Mykhaylo S Frasinyuk1, Wen Zhang, Przemyslaw Wyrebek

  • 1Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, USA. dwatt@uky.edu chunming.liu@uky.edu.

Organic & Biomolecular Chemistry
|September 5, 2017
PubMed

Insights

Cytisine-linked isoflavonoids (CLIFs) target the HSD17B4 enzyme, inhibiting prostate and colon cancer cell growth. This discovery highlights HSD17B4 as a potential cancer biomarker and therapeutic target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Cancer cell proliferation is a hallmark of tumor growth.
  • Identifying novel molecular targets is crucial for cancer therapy.
  • Peroxisomal enzymes play roles in cellular metabolism and disease.

Purpose of the Study:

  • To identify the molecular target of Cytisine-linked isoflavonoids (CLIFs).
  • To investigate the role of the identified target in prostate and colon cancer.
  • To evaluate CLIFs as potential therapeutic agents or research probes.

Main Methods:

  • Pull-down assays using biotin-modified CLIFs.
  • Enzyme activity assays with truncated HSD17B4.
  • Analysis of HSD17B4 expression in cancer tissues.
  • RNA interference (RNAi) to knockdown HSD17B4.

Main Results:

  • CLIFs specifically inhibit the peroxisomal enzyme hydroxysteroid 17β-dehydrogenase-4 (HSD17B4).
  • CLIFs bind to the C-terminus of HSD17B4 and inhibit its enoyl CoA hydratase activity.
  • HSD17B4 is overexpressed in prostate and colon cancer tissues.
  • Knockdown of HSD17B4 suppressed cancer cell proliferation.

Conclusions:

  • HSD17B4 is a validated target for inhibiting cancer cell proliferation.
  • HSD17B4 represents a potential biomarker and therapeutic target for prostate and colon cancers.
  • CLIFs show promise as novel therapeutic agents or research tools for these cancers.

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