Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9001
Title: Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.
Authors: Bahl, Deepa
Athar, Fareeda
Soares, Milena Botelho Pereira
Sá, Matheus Santos de
Moreira, Diogo Rodrigo Magalhães
Srivastava, Rajendra Mohan
Leite, Ana Cristina Lima
Azam, Amir
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
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 drugs
DNA
Entamoeba histolytica
Metal complexes
Plasmodium falciparum
Thiosemicarbazones
DeCS: Amebicidas/química
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
Issue Date: 2010
Publisher: Elsevier
Citation: BAHL, D. et al. Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities. Bioorganic & Medicinal Chemistry, v. 18, n. 18, p. 6857-6864, 2010.
ISSN: 1464-3391
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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