1,3-二甲基-4-酰基-5-吡唑酮二烃基锡抗癌配合物与单核苷酸作用的研究

目的研究1,3-二甲基-4-乙酰基-5-吡唑酮(HL₁)的二烃基锡抗癌配合物在近生理条件下与单核苷酸和DNA的作用机制。方法以高分辨核磁共振研究有机锡化合物在不同时间、不同条件下与核苷酸的作用方式并用UV法进一步研究有机锡化合物与DNA的作用。 结果(L₁)₂SnEt₂与AMP作用时可引起AMP碱基上H(8),H(2)和³¹P峰化学位移值显著变化并可引起DNA增色效应;(L₁)₂SnMe₂与AMP作用时只引起AMP的³¹P化学位移值的显著变化,未观察到AMP的H(8)和H(2)化学位移值的明显改变,(L₁)₂SnMe₂与DNA的作用可导致DNA的减色效应;(L₁)₂SnEt₂和(L₁)₂SnMe₂在与dCMP和dGMP作用时只引起dCMP和dGMP的³¹P的化学位移数值的明显变化。结论 3-二甲基-4-乙酰基-5-吡唑酮的二乙基锡配合物(L₁)₂SnEt₂可与AMP的碱基N₁和磷酸根氧原子螯合并可能会破坏DNA的双股螺旋结构;而二甲基锡配合物(L₁)₂SnMe₂易与单核苷酸的磷酸氧结合,难以与单核苷酸的碱基氮原子稳定结合且只引起DNA双股螺旋的收缩。

STUDY OF THE INTERACTIONS BETWEEN DIORGANOTIN (IV) COMPLEXES OF 1,3-DIMETHYL-4-ACETYL-5-PYRAZOLONE AND MONONUCLEOTIDES AND DNA

AIM The interactions between diorganotin (IV) complexes of 1,3 dimethyl 4 acetyl 5 pyrazolone (HL 1) and mono nucleotides together with DNA near physiological condition were investigated. METHODS The mode of action of the diorganotin (IV) complexes with mononucleotides and DNA under different conditions and different times were investigated by high resolution NMR technology and UV spectra. RESULTS The interaction of [(L 1) 2SnEt 2] with AMP was shown to result in significant change of chemical shift of H(8), H(2) and 31 P of AMP. Hyperchromic effect of DNA could be observed due to the interaction of; [(L 1) 2SnEt 2] with DNA, while interaction of [(L 1) 2SnMe 2] with AMP and DNA could only cause obvious change of chemical shift of 31 P and lead to hypochromic effect of DNA. CONCLUSION The results indicate that [(L 1) 2SnEt 2] can selectively bind to the N 1 atom of the base and the phosphate oxygen atom of AMP and may further destroy the helical structure of DNA, while the dimethyltin(IV) compound of 1,3 dimethyl 4 acetyl 5 pyrazolone [(L 1) 2SnMe 2] merely binds to the the phosphate oxygen atom of AMP and causes the contraction of DNA helical structure.