Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.
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 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) 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.
Bahl
Deepa
D
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Athar
Fareeda
F
Soares
Milena Botelho Pereira
MB
de Sá
Matheus Santos
MS
Moreira
Diogo Rodrigo Magalhães
DR
Srivastava
Rajendra Mohan
RM
Leite
Ana Cristina Lima
AC
Azam
Amir
A
D000563:Amebicides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004748:Entamoeba histolytica / Q000187:drug effects; D008670:Metals / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D000563:Amebicides; D000962:Antimalarials; D056831:Coordination Complexes; D008670:Metals; D013882:Thiosemicarbazones