Original article New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity Shadia A. Galal a, * , Khaled H. Hegab b , Ahmed S. Kassab a , Mireya L. Rodriguez c , Sean M. Kerwin c , Abdel-Mo’men A. El-Khamry d , Hoda I. El Diwani a a Division of Pharmaceutical and Drug Industries, Department of Chemistry of Natural and Microbial Products, National Research Center, Cairo, Egypt b Division of Inorganic Chemical Industries and Mineral Resources, Department of Inorganic Chemistry, National Research Center, Cairo, Egypt c Division of Medicinal Chemistry, Department of Chemistry and Biochemistry, The University of Texas, Austin, TX 78712, USA d Faculty of Science, Department of Chemistry, Ein Shams University, Cairo, Egypt article info Article history: Received 1 June 2008 Received in revised form 8 July 2008 Accepted 11 July 2008 Available online 19 July 2008 Keywords: 2-Methylbenzimidazole Transition metal complexes Antitumor activity abstract Metal complexes of 2-methyl-1H-benzimidazole-5-carboxylic acid hydrazide (4a;L 1 ) and its Schiff base 2-methyl-N-(propan-2-ylidene)-1H-benzimidazole-5-carbohydrazide (5a;L 2 ) with transition metal ions e.g., copper, silver, nickel, iron and manganese were prepared. The complexes formed were 1:1 or 1:2 M:L complexes and have the structural formulae [Cu(L 1 )Cl(H 2 O)]Cl$3H 2 O(6), [Ag(L 1 )NO 3 (H 2 O)] (7), [Ni(L 1 )Cl 2 (H 2 O) 2 ]$H 2 O(8), [Fe(L 1 )Cl 3 (H 2 O)]$3H 2 O(9) and [Mn(L 1 ) 2 Cl(H 2 O)]Cl$3H 2 O(10) for ligand L 1 , and [Cu(L 2 )Cl 2 (H 2 O) 2 ]$H 2 O(11), [Ag(L 2 ) 2 ]NO 3 $H 2 O(12), [Ni(L 2 ) 2 Cl 2 ]$5H 2 O(13), [Fe(L 2 ) 2 Cl 2 ]Cl$2H 2 O(14) and [Mn(L 2 )Cl 2 (H 2 O) 2 ]$H 2 O(15) for ligand L 2 . The antitumor activity of the synthesized compounds has been studied. The silver complex 7 was found to display cytotoxicity (IC 50 ¼ 2 mM) against both human lung cancer cell line A549 and human breast cancer cell line MCF-7. Ó 2008 Elsevier Masson SAS. All rights reserved. 1. Introduction Benzimidazole ring acts as ligand toward transition metal ions in a variety of biologically important molecules [1]. Cu(II) complex of CuL(ClO 4 ) 2 (L ¼ N,N,N 0 ,N 0 -tetrakis[2- benzimidazolyl)methyl]-1,3-diaminopropane (I) can electrostati- cally bind to the phosphate groups of DNA backbone and partially intercalate into the double helix of DNA [2]. N-Trimethylsilylpropylbenzimidazole (II) metal complexes exhibit cytotoxic activity on four monolayer tumor cell lines: MG-22A (mouse hepatoma), HT-1080 (human fibrosarcoma), B16 (mouse melanoma, Neuro 2A (mouse neuroblastoma)) and normal mouse fibroblast cells [3]. It was reported that some of the 2-substituted benzimid- azole Pt(II) complexes have in vitro cytotoxic activities on different cancer cell lines. cis-[Pt (R() and S(þ)-HBB) 2 Cl 2 ] (HBB ¼ 2-a-hydroxybenzylbenzimidazole) III and IV, respec- tively, were synthesized and have in vitro cytotoxic activities on the human MCF-7 breast cancer and HeLa cervix cancer cell lines [4–8]. * Corresponding author. Tel.: þ20 233371718; fax: þ20 233370931. E-mail address: sh12galal@yahoo.com (S.A. Galal). Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ – see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2008.07.013 European Journal of Medicinal Chemistry 44 (2009) 1500–1508