Synthesis of triazolopyridazine derivatives using iodobenzene diacetate and evaluation of their anticancer activity against MCF-7 breast cancer cells

Abstract

This study reports an efficient synthesis of 6-(4-methoxyphenyl)-3-aryl-[1,2,4]triazolo[4,3-b]pyridazine derivatives via oxidative cyclization of the corresponding hydrazones using iodobenzene diacetate as a mild and metal-free oxidizing agent. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, FTIR, and mass spectrometry. Their in vitro anticancer activity was evaluated against the MCF-7 breast cancer cell line, where four compounds (7a, 7c, 7d, and 7f) exhibited notable cytotoxic effects. Molecular docking studies suggested favorable binding interactions of these compounds with several cancer-related targets, including human 17β-hydroxysteroid dehydrogenase, topoisomerase IIα, p73 tetramerization domain, Bcl2-xL, EGFR tyrosine kinase, and survivin. Docking of the complete compound series (7a-7j) further supported the observed activity trends. These findings indicate that triazolopyridazine derivatives represent promising scaffolds for further investigation as anticancer agents. IBD was used as an environment friendly reagent for the synthesis of 1,2,4-triazolo[4,3-b]pyridazines by oxidative cyclization of hydrazone derivatives. 1,2,4-Triazoles showed excellent anticancer activity against breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. The molecular docking studies were carried out with several enzymes associated with breast cancer to find the effective binding of the synthesized compounds.