Exploring the Versatility of Cycloplatinated Thiosemicarbazones as Antitumor and Antiparasitic Agents

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 K2[PtCl4]. Two mononuclear (3 and 4) and two dinuclear (5 and 6) complexes were isolated upon cleavage of the Pt–Sbridging 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 β-hematin formation inhibition assays were also completed. Preliminary results suggest that ligand 1 and complex 3 do not hinder formation of β-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.

本研究以具有生物学意义的配体3,4-二氯苯乙酮硫代半卡巴腙（1）为原料，合成了三齿环铂化硫代半卡巴腙配合物（Tridentate cycloplatinated thiosemicarbazone complexes）。通过该配体与四氯合铂(II)酸钾（K2[PtCl4]）的反应，制备得到四核配合物2。将四核配合物2与合适的膦配体反应以断裂Pt-S桥键，分离得到2个单核配合物（3和4）以及2个双核配合物（5和6）。采用多种分析与光谱表征技术对所有配合物进行了结构表征，并解析了配合物2~4的分子结构。
测试了上述配合物对恶性疟原虫（Plasmodium falciparum）D10株（氯喹敏感株）、Dd2株（氯喹耐药株）以及阴道毛滴虫（Trichomonas vaginalis）的体外抗寄生虫活性。同时以β-血红素形成抑制实验为手段，开展了针对其潜在疟原虫作用靶点的初步研究。初步结果显示，配体1与配合物3不会阻碍β-血红素的形成。
此外，评估了该系列配合物对顺铂敏感型A2780和顺铂耐药型A2780cisR人卵巢癌细胞系的抗增殖活性，结果显示此类配合物仅表现出中等至微弱的抑制活性。