Abstract
The ideal drug discovery process of new platinum based drugs should take into account three basic fundaments: on one side the mechanisms of action and the corresponding target biomolecules, on the other side, the possible mechanisms of resistance of cancer cells and their biochemical pathways and, finally, the pharmacokinetic and toxicity properties (ADMET) that will condition the clinical usefulness of the new drugs. At the end of this rational process always we face the necessity to design a molecule with a structure and certain physical and chemical properties. The structure is then a key fundamental issue when thinking of new anticancer platinum compounds. When analyzing the influence of molecular structure on anticancer activity it is useful to make the dissection of platinum complexes into different significant subunits or moieties, of the molecular structure. Thus, the following structural and electron dependent parameters are important to facilitate the comparison among platinum complexes: a) Nature of the non-labile ligand or carrier ligand (NLG); b) Nature of the labile ligand or leaving group (LG); c) Oxidation state of platinum atom; d) Type of atoms (connecting atoms X, Y, Z, W) that link ligands to platinum atom; e) Nature of the axial groups (AG) in platinum(IV) complexes; f) Nuclearity or number of Pt atoms in the platinum complexes; g) Formal charges present in the molecule and h) Intrinsic bioactivity of some ligands or bioactivity induced by molecules attached to ligands by linkers (in order to get a double mechanism of action or a parallel biological activity).
Keywords: Platinum complexes, anticancer agents, SAR (structure-activity relationship), rational drug design
Current Medicinal Chemistry
Title: The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship
Volume: 16 Issue: 18
Author(s): Angel M. Montana and Consuelo Batalla
Affiliation:
Keywords: Platinum complexes, anticancer agents, SAR (structure-activity relationship), rational drug design
Abstract: The ideal drug discovery process of new platinum based drugs should take into account three basic fundaments: on one side the mechanisms of action and the corresponding target biomolecules, on the other side, the possible mechanisms of resistance of cancer cells and their biochemical pathways and, finally, the pharmacokinetic and toxicity properties (ADMET) that will condition the clinical usefulness of the new drugs. At the end of this rational process always we face the necessity to design a molecule with a structure and certain physical and chemical properties. The structure is then a key fundamental issue when thinking of new anticancer platinum compounds. When analyzing the influence of molecular structure on anticancer activity it is useful to make the dissection of platinum complexes into different significant subunits or moieties, of the molecular structure. Thus, the following structural and electron dependent parameters are important to facilitate the comparison among platinum complexes: a) Nature of the non-labile ligand or carrier ligand (NLG); b) Nature of the labile ligand or leaving group (LG); c) Oxidation state of platinum atom; d) Type of atoms (connecting atoms X, Y, Z, W) that link ligands to platinum atom; e) Nature of the axial groups (AG) in platinum(IV) complexes; f) Nuclearity or number of Pt atoms in the platinum complexes; g) Formal charges present in the molecule and h) Intrinsic bioactivity of some ligands or bioactivity induced by molecules attached to ligands by linkers (in order to get a double mechanism of action or a parallel biological activity).
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Cite this article as:
Montana M. Angel and Batalla Consuelo, The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship, Current Medicinal Chemistry 2009; 16 (18) . https://dx.doi.org/10.2174/092986709788453087
DOI https://dx.doi.org/10.2174/092986709788453087 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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