Physicochemical studies and biological chemistry of new metal chelates

Abstract

Medicinal inorganic chemistry- a sub area of bioinorganic chemistry is at the interface between medicine and inorganic chemistry. Since nature has made extensive use of metal ions in biological system, coordination chemists were inspired to explore the possibility of incorporating metal ions into drugs either by fortuity or by intention. This opened a new discipline of inorganic chemistry, metal-based drugs which was exponentially expanded by the serendipitous discovery of archetypical inorganic antitumor drug, cisplatin, cis-diamminedichloroplatinum(II) (as it contains not one atom of carbon) and its subsequent use for the treatment of solid malignancies viz; testicular, ovarian, small cell lung and colon cancers. The unique lesion made by platinum has not to date, been mimicked by any organic drug clearly emphasising the metal biomolecule interaction is critical to the antitumor activity of platinum as it is in general, for the activity of any other metallo-drug. Nevertheless, platinum drugs are effective only for a narrow spectrum of tumor cells (cancers are derived from many epigenetic origins and therefore exhibit various phenotypes); and are also associated with systemic toxicity issues and patient compliances. Therefore, discovering new metal-based drugs which are selectively active on cancerous cell life cycle, in an anti proliferative and/or pro apoptotic manner remain a challenge. Consequently, a large number of metal complexes have been designed and are currently under evaluation for chemotherapeutic applications. Many studies have been done to elucidate the mechanism of action as well as to optimize and improve the activity in comparison to platinum based drugs. newlineThe importance of ligand scaffold in modifying the biological effects of metal based drugs cannot be under estimated. Ligands can modify the oral / systemic newlinebioavailability of metal ions, can assist in targeting specific issues or enzymes, can deliver, protect or sequester a particular metal ion depending on the requirements