Metallo – Bioactive Pyridopyrazolopyrimidine Complexes as a new Class for Anticancer Therapy

M. I. Ayad1, W. A. Ragab2, Islam El-Garawani3, Mohammed H. H. Abu-Setta*1 and Noor Smah. S. Shams El-Dein1

1Department of Chemistry, Faculty of Science, Menoufia University, Shebin El -Kom, EGYPT. 2 Food Technology Research Institute, Agriculture Research Center, Giza, EGYPT. 3Zoology Department, Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, EGYPT.


The synthesis of bioactive pyridopyrazolopyrimidine ligands denoted I, II and III were described. The chelation abilities of the ligand towards Co(II), Cu(II( salts have been studied and give the following formula: [Cu(H2L1)(HL1)(CH3COO) (H2O)].3H2O, (Ib), [Cu(HL1)2(H2O)2].1.5H2O, (Ic), [Co(H2L1)2Cl(OH)].H2O, (Id), [Cu(H2L2)(OH)(H2O)].Cl.0.5H2O, (IIa), [Cu(HL3)Cl(H2O)2].H2O, (IIIa). These complexes of these ligands have much potential as anticancer agents. Chelates behave as a neutral bidentate ligand bonded to the metal ions through either the nitrogen atom of pyrazole ring and hydroxyl oxygen atom attached to pyrimidine ring or the nitrogen atom of amide group of pyrimidine ring and carbonyl oxygen atom of amide group of pyrimidine ring in protonated or deprotonated form. These structures have been synthesized and characterized by elemental analyses, (spectral method UV–Vis., IR), magnetic susceptibility, conductance and thermogravimetric analysis (TGA) were performed. Molar conductance in DMF arrangement demonstrates that, all complexes are non-electrolytes except the complex (IIa) is electrolyte. All these parameters described above, confirmed the proposed structures of these metal complexes. The safety and tolerance assessment of these complexes were done on normal peripheral blood leucocytes isolated from eight healthy non-smoker volunteers. Besides, the anticancer properties were evaluated on acute myeloid leukemia (AML) blasts of eight patients that were recently diagnosed for AML and received no chemotherapeutics until the samples were taken. The tested complexes should be investigated in depth towards other cancer cell lines to assess their possible integration as chemotherapeutics.

Keywords :Complexes, Synthesis, pyridopyrazolopyrimidines, Cytotoxicity.