ArticleAntimicrobial agents and chemotherapy2008
Antiplasmodial activity of [(aryl)arylsulfanylmethyl]Pyridine.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 56 citations in OpenAlex.
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- The MF6p/FhHDM-1 major antigen secreted by the trematode parasite Fasciola hepatica is a heme-binding protein.The Journal of biological chemistry · 2014Article
- Approaches towards the synthesis of a novel class of 2-amino-5-arylazonicotinate, pyridazinone and pyrido[2,3-d]pyrimidine derivatives as potent antimicrobial agents.Chemistry Central journal · 2013Article
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- Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum.Nucleic acids research · 2012Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) 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, H(2)O(2), and hydroxyl radical (.OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (DeltaPsim) 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 alpha-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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