Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine
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| Creator |
Kumar, Sanjay
Das, Sajal Kumar Dey, Sumanta Maity, Pallab Guha, Mithu Choubey, Vinay Panda, Gautam Bandyopadhyay, Uday |
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| Subject |
Infectious Diseases and Immunology
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| 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.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| 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. |
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| Relation |
http://dx.doi.org/10.1128/AAC.00898-07
http://www.eprints.iicb.res.in/285/ |
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