Metal compounds for the treatment of parasitic diseases

Fricker, Simon P.; Mosi, Renée; Cameron, Beth R.; Baird, Ian R.; Zhu, Youngbao; Anastassov, Virginia; Cox, Jennifer; Doyle, Patricia S.; Hansell, Elizabeth; Lau, Gloria; Langille, Jonathan; Olsen, Micki; Qin, Ling; Skerlj, Renato T.; Wong, Rebecca S.Y.; Santucci, Zefferino; McKerrow, James H.

doi:10.1016/j.jinorgbio.2008.05.010

Cited by 145 publications

(65 citation statements)

References 43 publications

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“…Other authors 25 observed that a palladacycle compound showed inhibition of the cysteine protease activity expressed in L. amazonensis amastigotes, being significant the inhibition of CpB activity. It was also reported that cyclometalled palladium(II) complexes 26 inhibited cathepsin B in other Leishmania species. However, the compounds did not affect the CpB activity of macrophages.…”

Section: Resultsmentioning

confidence: 87%

“…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. 24 Literature has reported a cyclopalladated compound with leishmanicidal activity 25 against L. amazonensis promastigote and amastigote forms; and the activity of some palladium(II) cyclometalated complexes 26 against T. cruzi and Leishmania, which indicate on preliminary data that the compounds inhibited the growth of intracellular amastigote forms.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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Section: Resultsmentioning

confidence: 87%

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

View full text Add to dashboard Cite

show abstract

“…The structure and function of this host organelle are reported to be highly affected by the parasitic attack. The pentavalent antimonial compound SAG are widely used as first-line chemotherapeutic 165,166 agents against all forms of leishmaniasis including visceral leishmaniasis 167,168 . In this work, we have assessed the status of host liver peroxisomes after the complete treatment of the L. donovani infected animals with standard dose of SAG.…”

Section: Discussionmentioning

confidence: 99%

“…In this work, we have assessed the status of host liver peroxisomes after the complete treatment of the L. donovani infected animals with standard dose of SAG. Peroxisomes were isolated by standard procedure 148 fr om normal hamters, al so fr om animals after Leishmania infection and from hosts after complete cure of the parasitic disease using conventional SAG treatment 169,170 . When parasite burden was measured two months after administration of the last dose, no parasite was detected in hamster spleen or liver, and that gave indication towards the complete cure of the disease.…”

Section: Discussionmentioning

confidence: 99%

Repair of Impaired Host Peroxisomal Properties Cropped Up Due to Visceral Leishmaniasis May Lead to Overcome Peroxisome Related Genetic Disorder Which May Develop Later After Treatment

Datta¹,

Gupta²,

Raychaudhury³

2011

Advances in the Study of Genetic Disorders

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“…Fricker et al [67] used a set of six Au(III) complexes, showing that all of them were able to inhibit cathepsin B, with a half maximal inhibitory concentration (IC 50 ) values in the range of 0.2-1.4 μM. Cysteine proteases cathepsin B play multiple roles in the parasite life cycle like nutrition, host invasion, protein processing, and evasion of the host immune response, so their inhibition can be extremely important.…”

Section: Nanogold Chemoterapymentioning

confidence: 99%

The role of nanogold in human tropical diseases: research, detection and therapy

Almeida

Carabineiro

2013

Gold Bull

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Metal compounds for the treatment of parasitic diseases

Cited by 145 publications

References 43 publications

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Repair of Impaired Host Peroxisomal Properties Cropped Up Due to Visceral Leishmaniasis May Lead to Overcome Peroxisome Related Genetic Disorder Which May Develop Later After Treatment

The role of nanogold in human tropical diseases: research, detection and therapy

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