Evaluation of in Vitro Antimicrobial and in Vivo Cytotoxic Properties of Some Novel Titanium-Based Coordination Complexes

Abstract

Metal coordination complexes had been widely studied for their antimicrobial 1) and anticancer properties. [2][3][4][5][6][7][8] Over the past 30 years, platinum-based drugs, notably cisplatin and carboplatin, have dominated the treatment of various cancers by chemical agents. McGowan 9) reported the first clinical trials of cisplatin in 1971, with official approval being granted in the US in 1978. By 1983, cisplatin was the US's biggest selling antitumour drug and is still one of those most widely used. It is one of the most effective drugs for treating testicular, ovarian, bladder and neck cancers. Despite the success of cisplatin, however, it lacks selectivity for tumour tissue, which leads to severe side effects. These include renal impairment, neurotoxicity and ototoxicity (loss of balance/hearing). Various tumor cell lines are now growing resistance to cisplatin, e.g., acquired cisplatin resistance in some (mainly murine) preclinical tumor models. 7) Recently there has been considerable interest and increased research activity in developing other transition metal compounds as anticancer drugs, which are less toxic than the platinum-based drugs. Among the other transition metal complexes the titanium complex, titanocene dichloride (TiCp 2 Cl 2 ) is the only metallocenebased compound to have entered clinical trials for its potent and broad spectrum activity in mammalian tumors. Compared to standard antineoplastic agents such as cisplatin, doxorubicin, mitoxantrone and vinblastine, titanocenedichloride was found to exhibit higher cytotoxicity in renal cell carcinoma.10) The titanocenedichloride was found to exhibit more efficacy in a human ovarian cancer xenograft model than cisplatin.11) Recently some derivatives of titanocenedichlorides showed enhanced anti-cancer activity. 12)Now scientists all over the world are seeking new titaniumbased complexes of potent anti-tumor effects with a different mode of action in the hope of adding new chemotherapeutic agents to the arsenal of weapons used against the world's most life threatening disease, i.e., cancer. Therefore, it is in our interest to study the antimicrobial and cytotoxic properties of some newly synthesized titanium(III) based complexes.The aim of this study was to determine the antimicrobial and cytotoxic activities of the newly synthesized titanium(III) complexes to identify their potent cytotoxic principles. We also evaluated the cytotoxicity of the titanium complexes in comparison with the anticancer agents, bleomycin and gallic acid. MATERIALS AND METHODS MaterialsThe coordination complexes were obtained from the Inorganic Chemistry Research Laboratory of Rajshahi University, Bangladesh, where these were prepared and characterized.13) The tested bacteria and fungi were obtained from the Microbiology Laboratory of the Institute of Nutrition and Food Sciences (INFS), University of Dhaka, Bangladesh. Preparation of Mixed Ligand Complexes of Ti(III) with Phthalimide or Succinimide and Amino acids[Ti(Pht/Suc) 2 (AA) 2 An aqueous solution of titanium chl...

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