Synthesis, Anticancer Activities and Molecular Docking Studies of a Novel Class of 2-Phenyl-5,6,7,8-tetrahydroimidazo [1,2- b]pyridazine Derivatives Bearing Sulfonamides

Molecules. 2022 Aug 17;27(16):5238. doi: 10.3390/molecules27165238.

Abstract

In the present study, new 2-phenyl-5,6,7,8-tetrahydroimidazo [1,2-b]pyridazines bearing sulfonamides were synthesized, characterized and evaluated for their anticancer activities. The structures of these derivatives were elucidated by 1H NMR, 13C NMR, infrared and high-resolution mass spectrometry for further validation of the target compound structures. The anticancer activities of the new molecules were evaluated against five human cancer cell lines, including A-549, Hs-683, MCF-7, SK-MEL-28 and B16-F10 cell lines using 5-fluorouracil and etoposide as the reference drugs. Among the tested compounds, 4e and 4f exhibited excellent activities in the same range of the positive controls, 5-fluorouracil and etoposide, against MCF-7 and SK-MEL-28 cancer cell lines, with IC50 values ranging from 1 to 10 μM. The molecular docking studies of 4e and 4f showed a strong binding with some kinases, which are linked to MCF-7 and SK-MEL-28 cancer cell lines.

Keywords: 2-phenyl-5,6,7,8-tetrahydroimidazo [1,2-b]pyridazine; anticancer activity; human cancer cell lines; sulfonamides.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Etoposide / pharmacology
  • Fluorouracil / pharmacology
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Neoplasms* / drug therapy
  • Pyridazines* / chemistry
  • Structure-Activity Relationship
  • Sulfanilamide / pharmacology
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use

Substances

  • Antineoplastic Agents
  • Pyridazines
  • Sulfonamides
  • Sulfanilamide
  • Etoposide
  • Fluorouracil

Grants and funding

This research was funded by the Euromed University of Fes and the University of Orleans.