Trávnícek Zdenek, Malon Michal, Zatloukal Marek, Dolezal Karel, Strnad Miroslav, Marek Jaromír
Department of Inorganic and Physical Chemistry, Palacký University, Krízkovského 10, CZ-771 47 Olomouc, Czech Republic.
J Inorg Biochem. 2003 Apr 1;94(4):307-16. doi: 10.1016/s0162-0134(03)00051-5.
The new square-planar Pt(II) and Pd(II) complexes with cytokinin-derived compounds Bohemine and Olomoucine, having the formulae [Pt(BohH(+))Cl(3)].H(2)O (1), [Pt(Boh)(2)Cl(2)].3H(2)O (2), [Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3), [Pt(OloH(+))Cl(3)].H(2)O (4), [Pd(BohH(+))Cl(3)].H(2)O (5), [Pd(Boh)Cl(2)(H(2)O)] (6), [Pd(Boh-H)Cl(H(2)O)].EtOH (7) and [Pd(OloH(+))Cl(3)].H(2)O (8), where Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)amino]-9-isopropylpurine and Olo=6-(benzylamino)-2-[(2-(hydroxyethyl)amino]-9-methylpurine, have been synthesized. The complexes have been characterized by elemental analyses, IR, FAB+ mass, 1H, 13C and 195Pt NMR spectra, and conductivity data. The molecular structure of the complex [Pt(BohH(+)-N7)Cl(3)].9/5H(2)O has been determined by an X-ray diffraction study. Results from physical studies show that both Bohemine and Olomoucine are coordinated to transition metals through the N(7) atom of purine ring in all the complexes. The prepared compounds have been tested in vitro for their possible cytotoxic activity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines and IC(50) values have been also determined for all the complexes. IC(50) values estimated for the Pt(II)-Bohemine complexes (2.1-16 microM) allow us to conclude that they could find utilization in antineoplastic therapy. Thus, from a pharmacological point of view, Pt(II) complexes of Bohemine may represent compounds for a new class of antitumor drugs.
已合成了新的具有细胞分裂素衍生化合物波希米宁（Bohemine）和奥洛莫辛（Olomoucine）的平面正方形铂（II）和钯（II）配合物，其化学式分别为[Pt(BohH(+))Cl(3)].H(2)O (1)、[Pt(Boh)(2)Cl(2)].3H(2)O (2)、[Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3)、[Pt(OloH(+))Cl(3)].H(2)O (4)、[Pd(BohH(+))Cl(3)].H(2)O (5)、[Pd(Boh)Cl(2)(H(2)O)] (6)、[Pd(Boh-H)Cl(H(2)O)].EtOH (7) 和 [Pd(OloH(+))Cl(3)].H(2)O (8)，其中Boh = 6-(苄基氨基)-2-[(3-(羟丙基)氨基]-9-异丙基嘌呤，Olo = 6-(苄基氨基)-2-[(2-(羟乙基)氨基]-9-甲基嘌呤。通过元素分析、红外光谱、快原子轰击正离子质谱、1H、13C和195Pt核磁共振光谱以及电导率数据对这些配合物进行了表征。通过X射线衍射研究确定了配合物[Pt(BohH(+)-N7)Cl(3)].9/5H(2)O的分子结构。物理研究结果表明在所有配合物中，波希米宁和奥洛莫辛均通过嘌呤环的N(7)原子与过渡金属配位。已对所制备的化合物针对G-361（人恶性黑色素瘤）、HOS（人骨肉瘤）、K-562（人慢性髓性白血病）和MCF-7（人乳腺腺癌）细胞系进行了体外细胞毒性活性测试，并测定了所有配合物的半数抑制浓度（IC(50)）值。对铂（II）-波希米宁配合物估计的IC(50)值（2.1至16 microM）使我们得出结论，它们可用于抗肿瘤治疗。因此，从药理学角度来看，波希米宁的铂（II）配合物可能代表一类新型抗肿瘤药物。
