STUDY OF THE ANTITUMORAL ACTIVITY OF A NEW Ru3+ COMPLEX: A PROPOSAL FOR THE METALOPHARMACEUTICAL DESIGN OF LOW TOXICITY

In this article the synthesis, characterization, acute toxicity, and antitumor activity of the novel Ru3+ complex are described. Through the acute toxicity tests, it was possible to fit the complexes into categories according to the OECD protocol guideline 423. The cisplatin complex was classified in category 1 and the sodium diaquodimalonateruthenate(3+) - Na[Ru(H2O)2(Mal-κ2O)2] - was classified in category 4. This result demonstrates the lower toxicity achieved by the ruthenium complex in comparison with metallopharmaceuticals compound. Evaluations of tumor masses extracted from mice inoculated with Ehrlich ascites carcinoma demonstrated percent inhibition lowest to cisplatin. Cisplatin showed 58% inhibition (1 mg/kg), while Na[Ru(H2O)2(Mal-κ2O)2] complex (5 mg/kg) presented 77%.本文详述了一种新型三价钌（Ru³+）配合物的合成、表征、急性毒性及抗肿瘤活性。通过急性毒性试验，可依据经济合作与发展组织（Organisation for Economic Co-operation and Development，OECD）423号试验指南对该配合物进行毒性分级：顺铂（Cisplatin）配合物被归为1级，而二水合二丙二酸合钌(Ⅲ)酸钠（Na[Ru(H₂O)₂(Mal-κ²O)₂]）被归为4级。该结果表明，与金属类药用化合物相比，该钌配合物的毒性更低。对接种艾氏腹水癌（Ehrlich ascites carcinoma）的小鼠所分离的肿瘤组织进行评估后发现，其肿瘤抑制率优于顺铂：顺铂在1 mg/kg剂量下的肿瘤抑制率为58%，而该Na[Ru(H₂O)₂(Mal-κ²O)₂]配合物在5 mg/kg剂量下的肿瘤抑制率可达77%。