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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Novel C,N-chelate rhodium(iii) and iridium(iii) antitumor complexes incorporating a lipophilic steroidal conjugate and their interaction with DNA
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Novel C,N-chelate rhodium(iii) and iridium(iii) antitumor complexes incorporating a lipophilic steroidal conjugate and their interaction with DNA

机译：新型C，N螯合铑（iii）和铱（iii）抗肿瘤复合物，结合了亲脂性甾体共轭物及其与DNA的相互作用

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摘要

The novel steroidal conjugates [M(η ~5-C _5Me _5)Cl(LEV-ppy)] (M = Rh (1) and Ir (2)) bearing the lipophilic levonorgestrel group 17-α-[2-phenylpyridyl-4-ethynyl]-19-nortestosterone (LEV-ppy), where the chelating ligand is N and C-bound, have been prepared and characterized. Both compounds are more active than cisplatin (about 6-fold) in T47D (breast cancer) at 48 h incubation time. On the other hand, very low resistance factors (RF) of 1 and 2 in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF = 0.9 and 1.1, respectively). The iridium steroidal compound 2 is twice as active as the non-steroidal analogue 2′, whose promising anticancer activity has recently been reported by Sadler. Theoretical DFT calculations on complexes 1 and 2 at the B3LYP-D/def2-TZVP-ecp level of theory show that the strongest bond to the metal atom is the η ~5-interaction to the Cp* ligand and that both of them feature a rather strong metal-chlorine bond. The new steroidal conjugates 1 and 2 are able to bind to DNA according to Hoechst 33258 displacement experiments and ESI-TOF MS spectrometry studies. Complexes 1 and 2 are also cathepsin B inhibitors, an enzyme implicated in a number of cancer related events.
机译：新型类固醇共轭物[M（η〜5-C _5Me _5Me_5）Cl（LEV-ppy）]（M = Rh（1）和Ir（2））带有亲脂性左炔诺孕酮基团17-α-[2-苯基吡啶基-4 -乙炔基] -19-睾丸激素（LEV-ppy），其中的螯合配体是N和C结合的，并已进行了表征。在48小时的孵育时间中，这两种化合物在T47D（乳腺癌）中的活性均比顺铂高（约6倍）。另一方面，在48小时时观察到A2780cisR（顺铂耐药卵巢癌）的耐药因子（RF）极低，分别为1和2（RF分别为0.9和1.1）。铱类固醇化合物2的活性是非类固醇类似物2'的两倍，Sadler最近报道了其有希望的抗癌活性。在B3LYP-D / def2-TZVP-ecp理论水平上对配合物1和2的理论DFT计算表明，与金属原子的最强键是与Cp *配体的η〜5-相互作用，并且两者都具有一个相当强的金属-氯键。根据Hoechst 33258置换实验和ESI-TOF MS光谱研究，新的甾体结合物1和2能够与DNA结合。配合物1和2也是组织蛋白酶B抑制剂，一种与许多癌症相关事件有关的酶。

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