J. Iran. Chem. Soc., Vol. 8, No. 4 December 2011, pp.983~991.

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Synthesis, Cytotoxicity and Calcium Antagonist Activity of Novel Imidazolyl Derivatives of 1,8-Acridinediones

A. Jamaliana, R. Mirib, O. Firuzib, M. Aminib, A.A. Moosavi-Movahedic and A. Shafieea,d,*

aDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran
bMedicinal and Natural Product Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz
cIran Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
dPharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

A series of  novel imidazolyl derivatives of fully and partially hydrogenated 1,8-acridinediones were synthesized and assessed for their cytotoxic activity on four different human cancer cell lines (HeLa, MCF-7, LS-180, and Raji cells). Although being inactive on LS-180 and Raji cell lines, the compounds showed weak to moderate anti-tumor activities on other cell lines and their IC50  ranged from  31.7 to more than 100 µM. Among the synthesized compounds 12b, 13b, 12c and 13c, bearing an electron-attracting substituent on the imidazole ring, and 12f and 13f, with a benzyl substituent, showed higher activities. Furthermore, the calcium channel antagonist activity of the derivatives, an undesired effect when these compounds are used as anti-tumor agents, was much lower than that of Nifedipine, a reference antagonist. Imidazolyl derivatives of 1,8-acridinedione represent an interesting template, showing promising biological properties. Further investigation on this chemical scaffold could potentially lead to the discovery of cytotoxic agents with low calcium channel blocking activity.

Keywords: Imidazole, 1,8-Acridinedione, Cytotoxicity, Calcium channel antagonist activity

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