Synthesis and Antitumor Activity of New 3-Allylseleno-6-alkoxypyridazines against Breast Cancer MCF-7 Cells

Abstract

Organoselenium compounds are useful reagents or synthons in organic synthesis. Over the past few years, synthetic strategies for selenium-containing heterocycles, novel selenium analogs of antioxidants, such as diphenyl diselenide, and Se-methylselenocysteine, which induces apoptosis through caspase activation in HL-60 cells, have been reported. The main components of volatile oils in garlic are sulfur compounds such as allicin. Allicin is responsible for the typical odor of garlic, but it is unstable and converts readily into other compounds. A number of sulfur compounds in garlic have been shown to possess anticarcinogenic activities. Through drug design, a pharmacologically active allylthio group was introduced into a pyridazine ring that is more stable. Various 3-allylthio-6-alkoxypyridazine derivatives (K-compounds) were synthesized by Kwon et al. 4 KCompounds showed especially good antitumor activities. We have reported on allylthio aralkylaminopyridazines and their anticancer activities. In these studies, allylseleno alkoxypyridazines, in which the sulfur atom of K-compounds was replaced with the selenium atom (Figure 1), were designed and synthesized as new organoselenopyridazines. The isosteric replacement of the sulfur of K-compounds by a selenium atom yields the allylselenopyridazines as target compounds. In order to discover potential anti-tumor organoselenium compounds, we designed new 3-allylseleno6-alkoxypyridazines 4a-4h. We synthesized new allylselenopyridazine derivatives that were expected to retain the anticancer activity. Target compounds were synthesized through the process of diselenylation, hydrolysis, Se-allylation and alkoxylation of starting material. We tested the ability of these synthetic compounds to inhibit the growth of human breast cancer MCF-7 Cell lines.