Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3',4':5,6][1,2,4]triazino[3,4- b][1,3,4]thiadiazine Derivatives

Molecules. 2018 Apr 27;23(5):1024. doi: 10.3390/molecules23051024.

Abstract

A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 310 and 1323, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data.

Keywords: antitumor activity; biological applications; cyclization reactions; pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclization
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Thiadiazines / chemical synthesis*
  • Thiadiazines / chemistry
  • Thiadiazines / pharmacology*

Substances

  • Antineoplastic Agents
  • Thiadiazines