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STRUCTURE-ACTIVITY RELATIONSHIPS OF MONONUCLEAR METAL-THIOSEMICARBAZONE COMPLEXES ENDOWED WITH POTENT ANTIPLASMODIAL AND ANTIAMOEBIC ACTIVITIES.
DNA
Entamoeba histolytica
Metal complexes
Plasmodium falciparum
Thiosemicarbazones
Antimaláricos/química
Complexos de Coordenação/química
Metais/química
Tiossemicarbazida/química
Amebicidas/síntese química
Amebicidas/toxicidade
Animais
Antimaláricos/síntese química
Antimaláricos/toxicidade
Complexos de Coordenação/síntese química
Entamoeba histolytica/efeitos de drogas
Camundongos
Plasmodium falciparum/efeitos de drogas
Baço/citologia
Baço/efeitos de drogas
Tiossemicarbazida/síntese química
Author
Affilliation
Jamia Millia Islamia. Department of Chemistry. Jamia Nagar, New Delhi, India
Jamia Millia Islamia. Centre for Interdisciplinary Research in Basic Sciences. New Delhi, India
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Pernambuco. Centre for Natural Sciences. Department of Fundamental Chemistry. Recife, PE, Brasil
Federal University of Pernambuco. Centre for Natural Sciences. Department of Fundamental Chemistry. Recife, PE, Brasil
Federal University of Pernambuco. Centre for Health Sciences. Department of Pharmaceutical Sciences. Recife, PE, Brasil
Jamia Millia Islamia. Department of Chemistry. Jamia Nagar, New Delhi, India
Jamia Millia Islamia. Centre for Interdisciplinary Research in Basic Sciences. New Delhi, India
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Pernambuco. Centre for Natural Sciences. Department of Fundamental Chemistry. Recife, PE, Brasil
Federal University of Pernambuco. Centre for Natural Sciences. Department of Fundamental Chemistry. Recife, PE, Brasil
Federal University of Pernambuco. Centre for Health Sciences. Department of Pharmaceutical Sciences. Recife, PE, Brasil
Jamia Millia Islamia. Department of Chemistry. Jamia Nagar, New Delhi, India
Abstract
A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive
ligands with transition metals. In view of this, an investigation was conducted into a new set of metal
complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance
of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized
furyl-thiosemicarbazones (NT1–4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the
mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological
characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity
to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure–activity relationship
data revealed that the metallic complexation plays an essential role in antiprotozoal activity,
rather than the simple presence of the ligand or metal alone. Important steps towards identification of
novel antiplasmodium (NT1Cu, IC50 of 4.6 lM) and antiamoebic (NT2Pd, IC50 of 0.6 lM) drug prototypes
were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation
of these parasites at concentrations that are not cytotoxic to mammalian cells.
Keywords
Antiparasitic drugsDNA
Entamoeba histolytica
Metal complexes
Plasmodium falciparum
Thiosemicarbazones
DeCS
Amebicidas/químicaAntimaláricos/química
Complexos de Coordenação/química
Metais/química
Tiossemicarbazida/química
Amebicidas/síntese química
Amebicidas/toxicidade
Animais
Antimaláricos/síntese química
Antimaláricos/toxicidade
Complexos de Coordenação/síntese química
Entamoeba histolytica/efeitos de drogas
Camundongos
Plasmodium falciparum/efeitos de drogas
Baço/citologia
Baço/efeitos de drogas
Tiossemicarbazida/síntese química
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