Quercetin Interferes With iron Metabolism in Leishmania donovani and Targets Ribonucleotide Reductase to Exert Leishmanicidal Activity
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Quercetin Interferes With iron Metabolism in Leishmania donovani and Targets Ribonucleotide Reductase to Exert Leishmanicidal Activity
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| Creator |
Sen, Gargi
Mukhopadhyay, Sibabrata Ray, Manju Biswas, Tuli |
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| Subject |
Cell Biology & Physiology
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| Description |
The possibility of developing antileishmanial drugs was evaluated by intervention in the
parasite’s iron metabolism, utilizing quercetin (Qr) under in vivo conditions, and identifying the target
of this lipophilic metal chelator against Leishmania donovani.
Methods: Interaction between Qr and serum albumin (SA) was studied by using the intrinsic fluorescence
of Qr as a probe. The effect of treatment with Qr and SA on the proliferation of amastigotes
was determined by evaluating splenic parasite load. Disintegration of parasites in response to combination
treatment was assessed from ultrastructural analysis using a transmission electron microscope.
Quenching of the tyrosyl radical of ribonucleotide reductase (RR) in treated amastigotes was detected
by an electron paramagnetic resonance study.
Results: Treatment with a combination of Qr and SA increased bioavailability of the flavonoid and
proved to be of major advantage in promoting the effectiveness of Qr towards the repression of
splenic parasite load from 75%, P < 0.01 to 95%, P < 0.002. Qr-mediated down-regulation of RR (P <
0.05), catalysing the rate-limiting step of DNA synthesis in the pathogens, could be related to the deprivation
of the enzyme of iron which in turn destabilized the critical tyrosyl radical required for its catalysing
activity.
Conclusions: Results have implications for improved leishmanicidal action of Qr in combination with
SA targeting RR and suggest future drug design based on interference with the parasite’s iron metabolism
under in vivo conditions.
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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/241/1/JOURNAL_OF_ANTIMICROBIAL_CHEMOTHERAPY%2C__61(5)%2C_1066%2D1075%2C_2008[85].pdf
Sen, Gargi and Mukhopadhyay, Sibabrata and Ray, Manju and Biswas, Tuli (2008) Quercetin Interferes With iron Metabolism in Leishmania donovani and Targets Ribonucleotide Reductase to Exert Leishmanicidal Activity. Journal of Antimicrobial Chemotherapy, 61 (5). pp. 1066-1075. |
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| Relation |
http://dx.doi.org/10.1093/jac/dkn053
http://www.eprints.iicb.res.in/241/ |
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