Synthesis, Spectral Characterization, and Antiproliferative Studies of Mixed Ligand Titanium Complexes of Adamantylamine

Raj Kaushal,Nitesh Kumar,Ashun Chaudhary,Saroj Arora,Pamita Awasthi

doi:10.1155/2014/142828

Abstract

Titanium complexes have been synthesized by the reaction between titanium tetrachloride (TiCl4), respective bidentate ligand [4,4′ -dimethoxy-2,2′ -bipyridine (bpome), 6,6′-dimethyl-2,2′-bipyridine (dpme), 1,2-diaminocyclohexane (dach), 1,10-phenanthroline (phen), and benzoylacetone (bzac)], and adamantylamine (ada) in 1 : 2 : 2 molar ratios, respectively. The structure of synthesized complexes was confirmed using elemental analysis, FTIR, UV-visible, 1H NMR, and mass spectrometry techniques. The nanocrystalline nature of complexes was confirmed by powder XRD study. The complexes were evaluated for cytotoxic potential in HeLa (cervical), C6 (glioma), and CHO (Chinese hamster ovarian) cell lines. The complex E was found to be more effective cytotoxic agent against HeLa cell line with an IC50 value of 4.06 µM. Furthermore, the effect of synthesized complexes was studied on different stages of the cell cycle in CHO cells. All complexes exhibited the dose dependent increase in cytotoxicity. The results have shown an increase in sub-G0 population with increase in concentration which is an indicative measure of apoptosis.

Highlights

The discovery of cisplatin, a metal based anticancer drug by Rosenberg et al in 1965, has created interest in the development of metal based anticancer drugs [1,2,3]
The effect of transition metal complexes, other than platinum such as ruthenium [4,5,6,7,8], palladium [9,10,11,12,13], gold [14, 15], and titanium [16,17,18,19,20,21,22,23,24,25] has been studied on several cancer cell lines
Since few efforts have been made towards the synthesis and use of titanium complexes as chemotherapeutic agents, this is an important area of research

Summary

Introduction

The discovery of cisplatin, a metal (platinum) based anticancer drug by Rosenberg et al in 1965, has created interest in the development of metal based anticancer drugs [1,2,3]. The effect of transition metal complexes, other than platinum such as ruthenium [4,5,6,7,8], palladium [9,10,11,12,13], gold [14, 15], and titanium [16,17,18,19,20,21,22,23,24,25] has been studied on several cancer cell lines. The first nonplatinum anticancer drugs were budotitane and titanocene dichloride which are titanium based drugs [16] These titanium complexes offer an alternative to chemotherapy, these complexes do not follow a mechanism similar to that of other metal complexes. Previous studies have revealed that titanium compounds are effective against those cell lines which are resistant to platinum based drugs and kill the cancer cells through apoptosis. We report the synthesis, structural characterization, and antiproliferative potential of some of titanium complexes

Experimental Section

Cytotoxicity Studies

Results and Discussion

Conclusions