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Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine

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Title Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine
 
Creator Kumar, Sanjay
Das, Sajal Kumar
Dey, Sumanta
Maity, Pallab
Guha, Mithu
Choubey, Vinay
Panda, Gautam
Bandyopadhyay, Uday
 
Subject Infectious Diseases and Immunology
 
Description A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited
hemozoin formation, formed complexes (KD � 12 to 20 �M) with free heme (ferriprotoporphyrin IX) at a pH
close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of
hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free
heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of
glutathione and increased formation of lipid peroxide, H2O2, and hydroxyl radical (·OH) in P. falciparum.
AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (��m) in malaria
parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of ·OH
may be mainly responsible for the antimalarial effect of AASMP since ·OH scavengers such as mannitol, as well
as spin trap �-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth
inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with
selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against
chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.
 
Date 2008
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/285/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY%2C_52(_2)%2C705%2D15%2C2008[126].pdf
Kumar, Sanjay and Das, Sajal Kumar and Dey, Sumanta and Maity, Pallab and Guha, Mithu and Choubey, Vinay and Panda, Gautam and Bandyopadhyay, Uday (2008) Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine. Antimicrobial Agents and Chemotherapy, 52 (2). pp. 705-715.
 
Relation http://dx.doi.org/10.1128/AAC.00898-07
http://www.eprints.iicb.res.in/285/