Evaluation of resistant-reversal, CDRI compound 87/209 and its possible mode of action in rodent experimental malaria.
The resurgence of malaria in form of resistance against chloroquine (CQ) has decreased the importance of the drug as a chemotherapeutic agent. If an agent in combination with CQ can make CQ resistant plasmodia susceptible to CQ, the problem of drug resistance may then be solved. Use of conventional drugs like verapamil, desipramine along with CQ suggested the feasibility of this approach. This report is concerned with a new class of compound, CDRI compound 87/209 (15 mg/kg b. wt.) which is given in combination with chloroquine (10 mg/kg b. wt.) for 10 consecutive days to chloroquine resistant P. berghei/P. yoelii nigeriensis (multidrug resistant) infected Mastomys coucha/Swiss albino mice respectively, displayed a potential in curing the animals. A tentative mode of action of the CDRI compound 87/209 based upon its unique property of inhibiting heme-oxygenase (a heme degrading enzyme) has been presented. It is likely that CDRI compound 87/209 in combination with chloroquine may reverse the resistance acquired by the malarial parasites and in combination with CQ is capable of clearing the parasite from the animals.
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
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R
Srivastava
V C
VC
Pandey
A P
AP
Bhaduri
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D009115:Muridae; D010860:Pigments, Biological / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects*; D010962:Plasmodium berghei / Q000187:drug effects / Q000378:metabolism; D010967:Plasmodium yoelii / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use*; D013045:Species Specificity; D014166:Transferases / Q000378:metabolism
D000962:Antimalarials; D006420:Hemeproteins; D010860:Pigments, Biological; D011759:Pyrrolidines; C081613:CDR 87-209; C020753:hemozoin; D006418:Heme; D002738:Chloroquine; D006419:Heme Oxygenase (Decyclizing); D014166:Transferases; C072176:heme polymerase