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BMC Chemical Biology 2006
Studies on the synthesis, characterization, binding with DNA and activities of two cis-planaramineplatinum(II) complexes of the form: cis-PtL(NH3)Cl2 where L = 3-hydroxypyridine and 2,3-diaminopyridineAbstract: Two cis-planaramineplatinum(II) complexes: cis-(3-hydroxypyridine)(ammine)dichloroplatinum(II) (code named AH3) and cis-(2,3-diaminopyridine)(ammine)dichloroplatinum(II) (code named AH7) have been prepared and characterised based on elemental analyses, IR, Raman, mass and 1H NMR spectral measurements. The interactions of the compounds with pBR322 plasmid DNA have been investigated and their activity against ovarian cancer cell lines: A2780, A2780cisR and A2780ZD047Rhave been determined. Like cisplatin, AH3 and AH7 are believed to form mainly monofunctional N7(G) and bifunctional intrastrand N7(G)N7(G) adducts with DNA, causing a local distortion of a DNA strand. As a result, gel mobility of the DNA changes. Both AH3 and AH7 are found to be less active than cisplatin against the three cell lines with AH3 being the more active compound of the two. The higher activity of AH3 is in line with its lower molar conductivity value corresponding to a lower degree of dissociation.The differences in activity of AH3, AH7 and cisplatin against the cell lines illustrate structure-activity relationship.Although cisplatin is a widely used anticancer drug [1,2], it has a number of side effects and a limited spectrum of activity [3-7]. In an attempt to reduce toxicity and widen the spectrum of activity thousands of cisplatin analogues have been prepared by varying the nature of the leaving groups and the carrier ligands [8]. By manipulating the structure the leaving groups it has been possible to reduce toxicity (eg substitution of the more stable cyclobutanedicarboxylate for the two chlorides led to the development of carboplatin which produces substantially less nausea, vomiting and neurotoxicity but causes more of myelosuppression) and that of the carrier ligands, it has been possible to achieve a limited change in the spectrum of activity (eg oxaliplatin which has 1,2-diaminocyclohexane as the carrier ligands has been found to be active against colorectal cancer whilst cisplatin i
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