Synthesis, structure, and in vitro anticancer activity of new polycyclic 1,2-diazines
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The synthesis, structure, and in vitro anticancer activity of a new class of anticancer derivatives with dihydrobenzo[5,6]isoindolo[1,2-a]phthalazine and dihydrobenzo[f]pyridazino[6,1-a]isoindole skeletons are presented. The preparation is straight and efficient, involving two steps only: a N-alkylation of the pyridazine or phthalazine heterocycle, followed by a [3 + 2] dipolar cycloaddition of 1,2-diazinium ylides to the corresponding dipolarophiles. The synthesis was performed under microwave and ultrasound (US) irradiation as well as under conventional thermal heating. The most effective conditions in term of yields and time were found to be US irradiation. The penta- and tetra-cyclic 1,2-diazines were evaluated for their in vitro anticancer activity. The pentacyclic 1,2-diazine derivatives exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM, and Breast Cancer MCF7. A feasible explanation for anticancer efficiency of the pentacyclic 1,2-diazines have been furnished, being correlated with the mechanisms of action.
KeywordsPolycyclic 1,2-diazines Cycloadditions Benzoquinone Anticancer
Authors are thankful to POSDRU Grant 89/1.5/S/49944, “Developing the innovation capacity and improving the impact of research through post-doctoral programs,” for financial support.
- Butnariu R, Risca IM, Caprosu M, Drochioiu G, Mangalagiu II (2008) Biological activity of some new pyridazine derivatives in wheat germination experiments. Rom Biotechnol Lett 13:3837–3842Google Scholar
- Hu FZ, Zang M, Zhu YQ, Zou XM, Liu B, Yang HZ (2007) Synthesis and herbicidal activity of 3-(substituted benzyloxy)-6-(substituted amino)pyridazines. Chin J Org Chem 27:1530–1536Google Scholar
- Mantu D, Maftei D, Iurea D, Bejan (Antoci) V (2012) Crystal structure of ethyl 5,10-dioxo-5,10-dihydrobenzo[f]pyridazino[6,1-a]isoindole-11-carboxylate. Rev Chim (Bucharest) 63:1239–1242Google Scholar
- Thurston DE (2007) Chemistry and pharmacology of anticancer drugs. CRC Press, New YorkGoogle Scholar
- US National Cancer Institute (NCI), Bethesda. http://dtp.nci.nih.gov/. Accessed 16 Dec 2012