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Synthesis of indazole based diarylurea derivatives and their antiproliferative activity against tumor cell lines

Cui-rong Zhao1, Rui-qi Wang, Gang Li

  • 1Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Wen Hua Xi Rd, Jinan 250012, China.

Bioorganic & Medicinal Chemistry Letters
|March 5, 2013
PubMed

Insights

New indazole-based diarylureas show potent anticancer activity, outperforming sorafenib against various cancer cell lines. Specific derivatives with trifluoromethyl or halogen substituents exhibit enhanced efficacy and lower toxicity.

Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis
  • Pharmacology

Background:

  • Diarylureas represent a significant class of compounds with demonstrated anticancer properties.
  • Sorafenib, a multi-kinase inhibitor, serves as a benchmark for anticancer drug efficacy.
  • Exploring novel chemical scaffolds is crucial for developing more effective cancer therapeutics.

Purpose of the Study:

  • To synthesize and evaluate a new series of indazole-based diarylurea derivatives for their anticancer potential.
  • To compare the efficacy of these novel compounds against a panel of human cancer cell lines with the established drug sorafenib.
  • To investigate the structure-activity relationships, particularly the influence of substituents on the indazole ring.

Main Methods:

  • Synthesis of a novel series of indazole-based diarylurea compounds.
  • In vitro anticancer activity screening against a diverse panel of human cancer cell lines (H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901, MDA-MB-231).
  • Acute toxicity assessment of select compounds and comparison with sorafenib.

Main Results:

  • Most synthesized indazole-based diarylureas demonstrated superior or comparable anticancer activity to sorafenib across multiple cell lines.
  • Derivatives featuring trifluoromethyl or halogen substituents on the indazole ring exhibited enhanced potency.
  • Compounds 5a, 5b, and 5i showed reduced acute toxicity compared to sorafenib, with compound 5i displaying the most significant anticancer effects.

Conclusions:

  • Indazole-based diarylureas represent a promising class of anticancer agents.
  • Strategic substitution on the indazole core, particularly with trifluoromethyl groups, can significantly enhance anticancer potency and potentially improve safety profiles.
  • Compound 5i is identified as a lead candidate for further development due to its potent anticancer activity and favorable toxicity profile.

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