title: Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi.
abstract: Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) both enzymatically and chemically, and inhibited glutathione reductase activity. 7-Benzyl derivative, which was obtained by reduction of the olefin group in α,β-unsaturated ketone structure of BNTX, also exhibited CQ-resistance reversing effect, but its potency was significantly lower than that of BNTX. These outcomes suggested that the decrease in GSH level could be one of the mechanisms of CQ-resistance reversing effects induced by BNTX derivatives.
authors: School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors: Yoshinori
authors: Y
authors: Miyata
authors: Hideaki
authors: H
authors: Fujii
authors: Yuka
authors: Y
authors: Uenohara
authors: Seiki
authors: S
authors: Kobayashi
authors: Tsutomu
authors: T
authors: Takeuchi
authors: Hiroshi
authors: H
authors: Nagase
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016788:Plasmodium chabaudi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000962:Antimalarials; D001597:Benzylidene Compounds; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D002738:Chloroquine; D005980:Glutathione Reductase