Design,Synthesis And Biological Evaluation Of Chiral Novel Platinum Complexes

In recent years,in the clinical treatment of malignant tumors,platinum antitumor drugs have been regarded as the first-line drugs due to a series of advantages,such as the unique mechanism of antitumor,strong anti-tumor activities and wide antitumor spectrum.But the problems that platinum antitumor drugs existed widely side effects,drug resistance,cross resistance and so on,have limited its clinical application.Therefore,developing lower toxicity with higher effect and introduction of new drug vehicles are important developing directions of platinum antitumor drugs in the future.Some dinuclear platinum complexes show improved cytotoxicity in many human cancer celllines.Moreover,dinuclear platinum complexes can form multi-point bonding with DNA.This bonding force makes DNA more devastating and more difficult to repaired as the dinuclear platinum complexes' non-classical structure-activity relationship.Dinuclear platinum complexes can avoid the clinical defects of the classical platinum anti-tumor drugs in a certain extent.Cucurbi[n]urea and its derivatives are one of the hot areas of supramolecular chemistry.They are widely studied in the application of molecular recognition,function and self-assembly.When cucurbi[n]urea and its derivatives serve as drug carrier,they could not only improve the water solubility and bioavailability of poorly soluble drugs but also to a certain extent,reduce drug side effects.Based on above considerations,this master's thesis is divided into two parts:1?Six novel dinuclear platinum complexes which with DNA intercalators were designed,synthesized and their anti-tumor activities in vitro were studied.Based on trans-1R,2R-cyclohexanediamine of chiral ligand of oxaliplatin.benzene ring of planar aromatic molecules with inserted effects,six novel dinuclear platinum(?)complexes with a tetradentate ligand.HL,have been designed,synthesized and characterized.To characterize the intermediate[Pt2I4L]and compounds A1-A6 IR.1H NMR,TG,MTT,ESI-MS spectroscopies and elementanalysis were applied.The newly synthesized compounds possessed DNA unwinding capability similar to cisplatin by the means of agarose gel electrophoresis,we screened out that the binuclear platinum complex A2 displayed the best antitumor effect in vitro and worth studying deeply.2?The new drug delivery system between platinum-based anticancer drugs with supramolecular macrocyclic host molecules cucurbit[7]uril were designed,synthesized and their anti-tumor activities in vitro were studied.The inclusion complexation behavior of cucurbit[7]uril with two platinum compounds molecule have been prepared.The chemistry stoichiometry and binding constant of cucurbit[7]uril with two platinum compounds were studied by fluorescence spectroscopy and Job's method.The complexes behaviors and inclusion mode investigated bv 1H and 2D NMR spectroscopy,differential scanning calorimetry,X-ray diffraction,and scanning electron microscopy.