Exploring the Versatility of Cycloplatinated Thiosemicarbazones as Antitumor and Antiparasitic Agents
Exploring the Versatility of Cycloplatinated Thiosemicarbazones as Antitumor and Antiparasitic Agents
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DOI：
10.1021/om300334z
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发表时间：
2012-08-27
期刊：
影响因子：
2.8
通讯作者：
Smith, Gregory S.
中科院分区：
文献类型：
--
作者：
Chellan, Prinessa;Land, Kirkwood M.;Smith, Gregory S.
由具有重要生物学意义的配体3,4-二氯苯乙酮硫代氨基脲制备了三齿环铂化硫代氨基脲配合物(1)。配体与K-2[PtCl4]反应制备了四核配合物2。用合适的膦配体切割四核配合物2的pt - s桥键，分离出两个单核配合物（3和4）和两个双核配合物（5和6）。利用各种分析和光谱技术对每个配合物进行了表征，并对2-4的分子结构进行了阐明。测定了这些复合物对恶性疟原虫(D10（氯喹敏感）和Dd2（氯喹耐药）和阴道毛滴虫的体外抗寄生活性。以β -血红素形成抑制试验的形式对其潜在的疟原虫靶点进行了初步研究。初步结果表明配体1和复合物3不妨碍β -血红素的形成。这些复合物对顺铂敏感的A2780和顺铂耐药的A2780cisR人卵巢癌细胞系的抗增殖活性已被评估。这些复合物表现出中等到弱的抑制活性。
Tridentate cycloplatinated thiosemicarbazone complexes have been prepared from a biologically significant ligand, 3,4-dichloroacetophenone thiosemicarbazone (1). The tetranuclear complex 2 was prepared by reaction of the ligand with K-2[PtCl4]. Two mononuclear (3 and 4) and two dinuclear (5 and 6) complexes were isolated upon cleavage of the Pt-S-bridging bonds of the tetranuclear complex 2 with the appropriate phosphane ligand. Each complex was characterized using various analytical and spectroscopic techniques, and the molecular structures of 2-4 were also elucidated. The in vitro antiparasitic activities of these complexes against Plasmodium falciparum strains (D10 (chloroquine sensitive) and Dd2 (chloroquine resistant)) and Trichomonas vaginalis have been determined. Preliminary studies into their potential plasmodial target in the form of beta-hematin formation inhibition assays were also completed. Preliminary results suggest that ligand 1 and complex 3 do not hinder formation of beta-hematin. The antiproliferative activity of the complexes against the cisplatin-senstive A2780 and cisplatin-resistant A2780cisR human ovarian cancer cell lines has been evaluated. The complexes were found to exhibit moderate to weak inhibitory activities.