Recebido em 31/3/98; aceito em 10/9/98 SYNTHESIS AND CYTOTOXICITY OF SOME CYCLOMETALLATED PALLADIUM(II) COM-PLEXES CONTAINING COORDINATED AZIDE AND DIPHOSPHINES. Some cyclopalladated compounds containing the azido group ligand and the (C-N) ring of N,N-dimethylbenzylamine have been prepared by bridge opening reactions of dimmer azide complex precursor with some diphosphines in different stoichiometric quantities. The neutral or ionic, mono or binuclear complexes synthesized were characterized by elemental analyses, I. R. spectroscopy and NMR techniques. The series of complexes was screened for cytotoxicity against a panel three human tumour cells lines(C6,Hep-2,HeLa). All complexes were found to be cytotoxic (IC 50 ) at µM concentrations while one complex having the coordination bond N-Pd ruptured also displayed some differential cytotoxicity.Keywords: azido-cyclopalladated compounds; antitumour agents; palladium (II) complexes. ARTIGO INTRODUÇÃOA eficácia da cisplatina cis-[Pt(NH 3 ) 2 Cl 2 ] e da carboplatina [Pt(NH 3 ) 2 (cbdca)], (cbdca =1,1'-ciclobutanodicarboxilato) no tratamento clínico de tumores do ovário, dos testículos, da cabeça e do pescoço já é bem conhecida 1 . Entretanto existe um grande interesse no desenvolvimento de novos agentes quimioterápicos a base de metais de transição, especialmente de metais pertencentes ao grupo da platina, que sejam menos tóxicos e, ou possuam um espectro de atividade antitumoral mais amplo 2 .Embora o mecanismo de ação dessas drogas seja muito discutido é amplamente aceito no meio científico que tanto a cisplatina quanto a carboplatina possuem o mesmo tipo de atuação na inibição do DNA da célula tumoral, provocando o mesmo tipo de lesão nesta molécula, formando um aduto G-G entre as cadeias de nucleotídeos laterais, que configuram a sua estrutura de dupla hélice 3-4 . Assim sendo, segue que estes compostos apresentam um espectro de atividade similar.Uma das estratégias básicas no desenvolvimento de novas drogas antitumorais a base de metais de transição consiste na síntese de complexos que, mesmo possuindo características estruturais similares a carboplatina ou a cisplatina, sejam capazes de provocar lesões diferentes e irreversíveis na molécula de DNA. No que concerne aos complexos de paládio, observase que os mesmos, em geral, possuem uma atividade antitumoral muito pequena quando comparado aos complexos de platina, devendo-se isto a alta labilidade exibida pelos compostos de paládio (II) em meio biológico 5 . Neste sentido, a classe dos compostos ciclopaladados tem despertado um recente e grande interesse na aplicação dos mesmos como agentes antineoplási-cos, não só por produzirem complexos estáveis o suficiente para permitirem uma eficaz ação da droga no organismo em concentrações muito baixas, mas também por possuirem uma citotoxicidade consideravelmente menor que os compostos aná-logos de platina [5][6][7][8] .O presente trabalho apresenta a síntese e a caracterização estrutural de alguns azido -ciclopaladados estabilizados com bases moles de Lewis 9 , contend...

The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(dmba)(μ-Cl)] 2 , [Pd(dmba)(NCO)(isn)], [Pd(dmba)(N 3 )(isn)] and [Pd(dmba)(μ-NCO)] 2 , (dmba: N,N'-dimethylbenzylamine and isn: isonicotinamide), against the diseases leishmaniasis (Leishmania amazonensis and Leishmania infantum), Chagas disease (Trypanosoma cruzi) and human African trypanosomiasis (Trypanosoma brucei). [Pd(dmba)(μ-NCO)] 2 exhibited good leishmanicidal and trypanocidal activities against L. amazonensis and T. cruzi intracellular amastigote forms, with a 50% inhibitory concentration (IC 50 ) value of less than 9 μM and selectivity indexes of 14.47 and 28.42, respectively. Stability essays were conducted in phosphate buffer saline (PBS) pH 7.0 and showed that [Pd(dmba)(μ-NCO)] 2 is the most stable molecule. These findings indicate that this compound presented higher selectivity for these parasites than the other tested compounds. The data presented here suggest that this compound should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas disease. 7 Pentavalent antimonial drugs are the most frequently prescribed treatments for leishmaniasis. 8 The main adverse effects that occur in systemic administration of these antimonials are arthralgias, myalgias, anorexia, and nausea, and other serious side effects include pancreatitis, liver-enzyme abnormalities, cardiac malfunctions and severe renal toxic effects. Other drugs, such as amphotericin B, pentamidine and miltefosine, are second choice drugs but they also produce side effects that can endanger the patient's life. KeywordsTrypanosoma cruzi is the causative agent of Chagas disease, which is present mainly in Latin America but also in North America. [10][11][12] Nifurtimox and benznidazole are the only drugs available to treat patients in the acute phase of the disease.13,14 However, these drugs are not Velásquez et al. 1033 Vol. 27, No. 6, 2016 effective against the chronic phase of the disease, and they present multiple side effects, from dermatitis to bone marrow depression. 15 HAT is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. 16Treatment of the hemolymphatic stage of HAT relies on suramin and pentamidine. In the meningoencephalitis stage, melarsoprol, a highly toxic arsenic-based drug that is effective against both T. b. gambiense and T. b. rhodesiense is used. Eflornithine is useful only against T. b. gambiense. An eflornithine/nifurtimox combined therapy has been used, but this also causes several side effects.17 In summary, the conventional drugs that have been employed to treat these diseases are antiquated, have high toxicity and are ineffective due to drug resistance. Therefore, is critical to develop new drugs for the treatment of these trypanosomiases.The use of transition metal-based drugs is increasing significantly in the therapy of cancer and tropical diseases; in fact, many organometallic compounds have been designed to specifically bind to a well-d...

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Metallointercalators represent a promising alternative in cancer chemotherapy. We present herein DNA binding, topoisomerase inhibition and cytotoxic studies on a series of complexes of general formulae [Pd (phen)(tu ⁄) 2 ] 2+ incorporating the intercalator 1,10-phenanthroline and thiourea ligands (L = thiourea 1, N-methylthiourea 2, N,N 0-dimethylthiourea 3). DNA-unwinding results showed that the complexes can induce the unwinding of the plasmid DNA. The binding constants (K b) for the interaction of the complexes with SS-DNA were determined by UV spectroscopy. Competitive experiments with ethidium bromide (EB) were investigated by fluorescence spectroscopy and show that all the complexes were able to displace EB from the DNA-EB complex. The results suggest that they may interact with DNA by intercalation. Compounds were tested against human oral carcinoma cell line (KB), human breast cancer cell line (MCF7) and cisplatin-resistant human breast cancer cell line (MCF7-R) and showed good cytotoxic activity towards MCF7-R. Compounds 2 and 3 were also able to cause topo II inhibition.

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