Trypanocidal and antitumour activity of platinum-metal and platinum-metal-drug dual-function complexes

Farrell, Nicholas; Williamson, J.; McLaren, Diane J.

doi:10.1016/0006-2952(84)90501-x

Cited by 77 publications

(41 citation statements)

References 22 publications

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“…Farrell et al [29] demonstrated that the antiparasite activity of a series of Pt(II) and Rh(III) complexes was greater than that shown by free ligands of these complexes. In addition, Steck [30] observed that the combination of pentamidine with anionic compounds gave rise to complexes with stronger prophylactic activity against the African trypanosomes.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Activity of New Rhodium (III) Complexes against Leishmania donovani

et al. 2001

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The activities of 17 new rhodium drug complexes were determined against Leishmania donovani promastigotes. The five most active salts were selected: [Rh^III(2-amino-6-ethoxybenzothiazole)₄Br₂]⁺Br^–; [Rh^III(2-bromothiazole)₄(Br)₂]⁺Br^–; [Rh^III(mefloquine)⁴(Cl)₂]⁺Cl^–; [Rh^III(2-mepacrine)₄(Cl)₂]⁺Cl^–, and [Rh^III(oxamniquine)₄(Cl)₂]⁺Cl^–, which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salts [Rh^III (mefloquine)₄(Cl)₂]⁺Cl^–, [Rh^III(2-mepacrine)₄(Cl)₂]⁺Cl^– and [Rh^III(oxaminquine)₄(Cl)₂]⁺Cl^– with a percentage of specific ¹⁵Cr release of 49.3, 64.8 and 53.2% at 24 h of incubation and 100 µg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The ultrastructural studies in the flagellates treated with the salt [Rh^III(2-amino-6-ethoxybenzothiazole)₄Br₂]⁺Br^– showed some alterations in the nucleus of the parasites with a very condensed chromatin and an electrodense endosome. This compound showed a high in vivo activity in parasitized Wistar rats.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Activity of New Rhodium (III) Complexes against Leishmania donovani

et al. 2001

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“…Farrell et al [22] demonstrated that the antiparasite activity of a series of Pt(II) and Rh(III) complexes was greater than that shown by free ligands of these complexes. In addition, Steck [23] observed that the combination of pentamidine with anionic compounds gave rise to complexes with stronger prophylactic activity against the African trypanosomes.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Activity of Two Pt(IV) Salts against Leishmania donovani

et al. 1998

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The activities of 8 platinum drug complex salts were determined against Leishmania donovani promastigotes. The three most active salts were selected: [Pt^IVBr₆]H₂ (pentamidine); [Pt^IVBr₆]H₂ (stilbamidine), and [Pt^IVCl₆]H₂ (2-piperazinyl(1) ethyl amine), which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salt [Pt^IVBr₆]H₂ (stilbamidine) with a percentage of specific ⁵¹Cr release of 58.2% at 24 h of incubation and 100 µg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The salt [Pt^IVBr₆]H₂ (pentamidine) notably inhibited the incorporation of ³H-thymidine in the treated parasites. The ultrastructural alterations observed in the flagellates treated with the salts [Pt^IVCl₆]H₂ (2-piperazinyl(1)ethyl amine) and [Pt^IVBr₆]H₂ (pentamidine) suggest that both act preferentially at the nuclear level and at the kinetoplast-mitochondrion complex. Both compounds showed a high in vivo activity in parasitized Wistar rats.

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“…[18][19][20] The emergence of drug resistance in tropical diseases has led to alternatives to chloroquine and its analogues, such as metallocene derivatives for the treatment of malaria. 19,20 Several scaffolds of metal complexes containing palladium, platinum, gold, iridium, rhodium, osmium and iron have shown leishmanicidal [18][19][20][21] and trypanocidal 22,23 activity. For palladium compounds, it was recently verified that a cyclopalladated complex showed a high selectivity index with trypanocidal activity in the treatment of Chagas disease.…”

Section: Introductionmentioning

confidence: 99%

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Velásquez¹,

Souza²,

Passalacqua³

et al. 2015

Journal of the Brazilian Chemical Society

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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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Trypanocidal and antitumour activity of platinum-metal and platinum-metal-drug dual-function complexes

Cited by 77 publications

References 22 publications

In vitro and in vivo Activity of New Rhodium (III) Complexes against <i>Leishmania donovani</i>

In vitro and in vivo Activity of New Rhodium (III) Complexes against <i>Leishmania donovani</i>

In vitro and in vivo Activity of Two Pt(IV) Salts against <i>Leishmania donovani</i>

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

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