The Anti-tumor Activity Of Rare Earth-curcumin-pyridine/2,2’-bipyridine/1,10-phenanthroline Complexes

With the development of modern science and technology and the further researchon biological resources, new drugs’ research focus increasingly turn to thedevelopment and utilization of natural products. Curcumin is a kind of yellowpigment which extracted from zingiberaceae plants such as the rhizome of turmeric,rhizoma zedoariae and so on, exists in other zingiberaceae plants widely, often used asfood colorants and meat pH indicator, also has the antioxidant and anti-inflammatory,antibacterial and other physiological and pharmacological activities. More recentstudies suggest that curcumin is an effective anti-mutagenic agent, it is also a promotecancer resistant agent, curcumin have obvious inhibitory effect on a variety of tumorcells. Rare earth ions also have certain pharmacological activities, such asanti-inflammatory, antiseptic, anti-cancer, anticoagulant pharmacological effects, etc.Our group has studied the rare earth-curcumin complexes and antimicrobial activityof rare earth-curcumin-1,10-phenanthroline complexes.The thesis aims to learn the effect of plane size of molecular on the growth ofcancer cells of HepG2. The binary and ternary complexes of rare earth (III) nitratehave been synthesized with the first ligand curcumin and the second ligand Pyridine,2,2-bipyridyl,1,10-phenanthroline in alcohol solution (pH=6.5~7.0,RE=Eu, La, Ce,Nd, L=curcumin, L′=Pyridine, L′′=2,2-bipyridyl, L′′′=1,10-phenanthroline). Thecomposition of the complexes includes REL3·2H2O and REL3L′2, REL3L′′andREL3L′′′. By a method of methyl thiazolyl tetrazolium(MTT),16kinds of complexes,RE(III) and curcumin on the inhibition of proliferation of HepG2cells are identified.The anti-tumor activity of the complexes on HepG2cells doesn’t increase whenthe aromatic plane increases in molecular. The results of the interaction of DNA withNd-complexes show this complexes have different interaction type with DNA. Theresults of metal complexes as anticancer drugs screening and discovery provides theexperimental basis.In order to further probing into the cause of the antitumor activity of thecomplexes, studied the effect of Nd-curcumin ternary complexes with DNA byfluorescence method, the results show that NdL3L’’ and NdL3L’’’ insert of the DNAmolecules, NdL3L’2have no insert function, the research results of this article provides the experimental basis for Screening and finding metal complexes as theanticancer drugs.This thesis consists of four parts:Part one: literature review.Curcumin is a kind of natural active substance, multi-effect have manypharmacological functions, it has widely application value on medicine, curcumin asactive ingredient of curcuma, effect on the each system of body widely; Rare earthions as determined by the nature of the all is because of the rare earth element itself,enhance will anti-cancer ability; Pyridine ring has the ability to enhance drugcombined with biological macromolecules, and pyridine compounds also have certainanti-tumor effect; So far, about2,2’-pyridine complexes biological activity ofliterature is not much, more is2,2’-pyridine binary and ternary transition metalmononuclear complexes.1,10-phenanthroline has great aromatic ring rigidity, itsderivative complexes as DNA secondary structure as the research and design fornucleic acid targets of anti-cancer drugs a kind of important compounds. Cancer is acommon disease and frequently encountered disease in a serious threat to human life,its mortality rate is second only to cardiovascular disease and in second place. Foundthat the selective effects on specific targets of high efficiency, low toxicity and strongspecificity of new anti-cancer drugs has become important in today’s anti-tumor drugsresearch and development direction.Part two: the synthesis and characterization of the rare earths-curcumin binary andternary complexes.In ethanol solution (pH=6.5~7.0) synthesized by four kinds of rare earthelements (RE=Eu, La, Ce, Nd) with curcumin (L), pyridine (L’),2,2-pyridine (L′′),1,10-phenanthroline (L′′′)complexes. By elemental analysis, molar conductance,thermogravimetric and differential thermal analysis, IR, UV-Vis method, to determinethe chemical composition of rare earth curcumin binary complexes as: REL3·2H2O;The chemical composition of the ternary complexes were respectively: REL3L′2,REL3L′′and REL3L′′′, and the characterization, analyses the thermal stability andthermal decomposition behavior of these complexes.Part three: antitumor activity research of rare earth curcumin binary and ternary complexesStudied the antitumor activity of Rare earth-curcumin binary and ternarycomplexes. Antitumor activity results show that ligands of curcumin, rare earthternary, binary complexes have some inhibitory effect on cancer cell growth, multiplecomplexes have obvious inhibitory effect on tumor HepG2, part of the complexesshows strong anticancer activity. REL3L’’’complexes inhibitory effect under thecondition of same test often stronger than the other complexes; Nd the three kinds ofternary complexes of inhibitory effect of similar complexes in the other three kinds ofrare earth elements has always been the strongest, explain Nd elements of thesecomplexes are potential practical value of antineoplastic drugs; Within the scope ofthe concentration of the test,often appear the phenomenon that REL3L complexesinhibitory effect than REL3L’2complexes, REL3·2H2O is stronger than of someternary complexes.Part four: Antibacterial sex research of rare earth curcumin complexes and theinteraction with DNATo further explorimg the mechanism of antitumor complexes, used thefluorescence method to study the effect of the complexes with DNA, the studyexamines the rare earth neodymium-curcumin-pyridine, rare earthneodymium-curcumin-2,2′-pyridine complexes, rare earthneodymium-curcumin-1,10-phenanthroline complexes and the interaction of DNA.Results showed that the NdL3L’’and NdL3L’’’to insert DNA molecules, NdL3L’2noinsert function. With neodymium-curcumin-pyridine, increased concentration ofternary complexes has had the obvious hyperchromic effect of DNA, uv absorptionspectrum, the results show that neodymium-curcumin-pyridine ternary complexescomplexes can lead to damage the DNA double helix structure.