Molecular design, synthesis and anticancer activity of new thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone)

Eur J Med Chem. 2023 Apr 5:252:115304. doi: 10.1016/j.ejmech.2023.115304. Epub 2023 Mar 24.


A series of 11-substituted 9-hydroxy-3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones 3.1-3.13 were synthesized via hetero-Diels-Alder reaction of 5-ene-4-thioxo-2-thiazolidinones and 5-hydroxy-1,4-naphthoquinone (juglone). The structure of newly synthesized compounds was established by means of spectral data and a single-crystal X-ray diffraction analysis. The synthesized compounds were tested on a panel of cell lines representing different types of cancer as well as normal and pseudonormal cells and peripheral human blood lymphocytes. Compound 3.10 was found to be the most active derivative, exhibiting a cytotoxic effect similar to doxorubicin's one (IC50 ranged from 0.6 to 5.98 μM), but less toxic to normal and pseudonormal cells. All synthesized compounds were able to interact with DNA, although their anticancer activity did not correlate with the potency of interaction with DNA. The status of p53 in colorectal cancer cells correlated with the activity of the synthesized derivatives 3.1, 3.7, and 3.10. Compound 3.10 did not have an acute toxic effect on the body of С57BL/6 mice, unlike the well-known anticancer drug doxorubicin, which was used as a positive control. The injection of 3.10 (20 mg/kg) to mice had no effect on the counts of leukocytes, erythrocytes, platelets and hemoglobin level in their blood, in contrast to doxorubicin, which caused anemia and leukopenia, indicating bio-tolerance of 3.10in vivo.

Keywords: Anticancer activity; Apoptosis; DNA interaction; Drug design; Juglone; Molecular docking; Thiopyranothiazoles.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Cell Line, Tumor
  • Cell Proliferation
  • Doxorubicin / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • Naphthoquinones* / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / chemistry


  • juglone
  • Thiazoles
  • Antineoplastic Agents
  • Naphthoquinones
  • Doxorubicin