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Updated: Apr 6, 2026

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
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Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade

Published on: August 14, 2019

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Rational design and synthesis of flavonolactam derivatives as potent topo I inhibitors with antitumor activity

Xiaoyu Shi1, Yaoguang Huang1, Xupeng Yang1

  • 1School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.

European Journal of Medicinal Chemistry
|April 4, 2026
PubMed

Insights

New flavonolactam derivatives show promise for colorectal cancer treatment. Compound NL-26 effectively inhibits topoisomerase I (Topo I), suppresses tumor growth in models, and warrants further investigation.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • Topoisomerase I (Topo I) is a key target for colorectal cancer (CRC) therapy.
  • Developing novel inhibitors with improved efficacy and pharmacokinetic profiles is crucial.

Purpose of the Study:

  • To design, synthesize, and evaluate novel flavonolactam derivatives as Topo I inhibitors for CRC.
  • To investigate the mechanism of action and in vivo efficacy of promising compounds.

Main Methods:

  • Synthesis of a series of flavonolactam derivatives.
  • In vitro evaluation of Topo I inhibitory activity and cell cycle arrest.
  • Apoptosis induction assays.
  • In vivo pharmacokinetic and antitumor efficacy studies in HCT116 xenograft models.

Main Results:

  • Compounds NL-26 and NL-28 demonstrated potent Topo I inhibition.
  • NL-26 exhibited strong Topo I inhibitory activity, comparable to camptothecin (CPT).
  • NL-26 showed favorable pharmacokinetics (AUC 1979.7 µgh/mL, t1/2 3.7 h) and significant antitumor efficacy (55.1% TGI) in vivo.

Conclusions:

  • NL-26 is identified as a promising lead compound for CRC therapy.
  • The flavonolactam scaffold is validated as a valuable template for developing novel Topo I inhibitors.
Keywords:
CPTCRCFlavonolactam derivativesTopo I

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