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ChemMedChem
Volumn 6, Issue 9, 2011, Pages 1603-1615
A partial convergence in action of methylene blue and artemisinins: Antagonism with chloroquine, a reversal with verapamil, and an insight into the antimalarial activity of chloroquine
Author keywords

Artemisinins; Chloroquine; Cofactor model; Methylene blue; Verapamil
Indexed keywords

ARTEMETHER; ARTEMISININ; ARTEMISONE; ARTESUNATE; ASCORBIC ACID; CHLOROQUINE; DICOUMAROL; DIHYDROARTEMISININ; FLAVINE ADENINE NUCLEOTIDE; METHYLENE BLUE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; RIBOFLAVIN; VERAPAMIL;
EID: 80052077892     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201100184     Document Type: Article
Times cited : (27)
References (93)
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    • + in enoyl-acyl carrier protein reductase, which is involved in the biosynthesis of mycolic acid in Mycobacterium tuberculosis. See:
    • + in enoyl-acyl carrier protein reductase, which is involved in the biosynthesis of mycolic acid in Mycobacterium tuberculosis. See:.
  • 19
    • 84857505739 scopus 로고    scopus 로고
    • 2, which in turn reduce methemoglobin to hemoglobin, a process that underpins the use of MB and RF for treatment of methemoglobinemia (Ref.[7] and references therein). The MB and RF thereby regenerated are reduced by NADPH-flavin reductase in continuation of the cycle. This underscores the potential importance of iron in enhancing redox cycling of these redox-active substrates, and of flavin cofactors such as FAD, of course. Similarly, iron enhances the antimalarial activities of artemisinins without chemically interacting with them (Ref.[7]).
    • 2, which in turn reduce methemoglobin to hemoglobin, a process that underpins the use of MB and RF for treatment of methemoglobinemia (Ref.[7] and references therein). The MB and RF thereby regenerated are reduced by NADPH-flavin reductase in continuation of the cycle. This underscores the potential importance of iron in enhancing redox cycling of these redox-active substrates, and of flavin cofactors such as FAD, of course. Similarly, iron enhances the antimalarial activities of artemisinins without chemically interacting with them (Ref.[7]).
  • 30
    • 67650679319 scopus 로고    scopus 로고
    • Both mammalian liver TrxR and malaria parasite apicoplast FNR display accelerated turnover of NADPH in the presence of artemisinins and appropriate substrates. FNR is functionally related to E. coli flavin reductase, and we have established that in the presence of NADPH, the parasite enzyme is also capable of reducing endogenous flavins, a reaction which, like the corresponding Fre reaction, is affected by artemisinin. This work will be reported separately. For preparation of the parasite FNR, see
    • Both mammalian liver TrxR and malaria parasite apicoplast FNR display accelerated turnover of NADPH in the presence of artemisinins and appropriate substrates. FNR is functionally related to E. coli flavin reductase, and we have established that in the presence of NADPH, the parasite enzyme is also capable of reducing endogenous flavins, a reaction which, like the corresponding Fre reaction, is affected by artemisinin. This work will be reported separately. For preparation of the parasite FNR, see: E. Balconi, A. Pennati, D. Crobu, V. Pandini, R. Cerutti, G. Zanetti, A. Aliverti, FEBS J. 2009, 276, 4249-4260.
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    • Balconi, E.1    Pennati, A.2    Crobu, D.3    Pandini, V.4    Cerutti, R.5    Zanetti, G.6    Aliverti, A.7
  • 80
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    • Iron and heme models are critically discussed in references[3] and [7] above, and in:
    • Iron and heme models are critically discussed in references[3] and [7] above, and in:.
  • 91
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    • Note added in proof: chloroquine competitively binds to the riboflavin binding protein associated with internalization and intracellular trafficking of RF required for the biosynthesis of FMN and FAD. This implies a separate antimalarial mode of action for chloroquine, given that such binding, if operating inside the malaria parasite, will act to suppress the biosynthesis of FAD. See
    • Note added in proof: chloroquine competitively binds to the riboflavin binding protein associated with internalization and intracellular trafficking of RF required for the biosynthesis of FMN and FAD. This implies a separate antimalarial mode of action for chloroquine, given that such binding, if operating inside the malaria parasite, will act to suppress the biosynthesis of FAD. See: A. Plantinga, A. Witte, M.-H. Li, A. Harmon, S. K. Choi, M. M. B. Holl, B. G. Orr, J. R. Baker, K. Sinniah, ACS Med. Chem. Lett. 2011, 2, 363-367.
    • (2011) ACS Med. Chem. Lett. , vol.2 , pp. 363-367
    • Plantinga, A.1    Witte, A.2    Li, M.-H.3    Harmon, A.4    Choi, S.K.5    Holl, M.M.B.6    Orr, B.G.7    Baker, J.R.8    Sinniah, K.9
  • 93
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    • Tabulated molar extinction coefficient for methylene blue in water: (accessed June 16, 2011).
    • Tabulated molar extinction coefficient for methylene blue in water: (accessed June 16, 2011).

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.