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

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

Rania S Ali  1   2 , Hosam A Saad  3   4
Affiliations

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

Rania S Ali et al. Molecules. .

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, 3⁻10 and 13⁻23, 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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Synthesis and some reactions on 3-hydrazinyl-7-(thiophen-2-yl)pyridazino[3,4-e][1,2,4]triazin-4(6H)-amine.
Scheme 2
Scheme 2
Some reactions on 4(6H)-amino-3-hydrazinyl-7-(thiophen-2-yl)pyridazino[3,4-e][1,2,4]triazine.
Scheme 3
Scheme 3
Synthesis and some reactions of 3-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile.
Scheme 4
Scheme 4
The mechanism of formation of compound 15.
Scheme 5
Scheme 5
Some reactions of 3-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile.
Scheme 6
Scheme 6
Mechanism of cyclization of compound 16.
Scheme 7
Scheme 7
Some reactions of 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.
Scheme 8
Scheme 8
Mechanism of formation of compound 22.
Scheme 9
Scheme 9
Mechanism of formation of compound 23.
Figure 1
Figure 1
The anti-tumor activities of the tested compounds expressed as IC50 values and compared with reference standard drugs evaluated on breast cancer, liver cancer, and colon carcinoma cell lines.
See this image and copyright information in PMC

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