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N ‐Malonyl‐1,2‐dihydroisoquinoline as a Novel Carrier for Specific Delivery of Drugs to the Brain
Author(s) -
AbdelAziz Mohamed,
AbuoRahma Gamal ElDin A. A.,
Hassan Heba A.,
Farag Hassan H.
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900109
Subject(s) - chemistry , pharmacology , combinatorial chemistry , stereochemistry , medicine
N ‐Malonyl‐1,2‐dihydroisoquinoline derivatives were synthesized and investigated as a novel carrier system for site‐specific and sustained delivery of drugs to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. Reduction of the prepared isoquinolinium quaternary derivatives with sodium dithionite afforded a novel group of N ‐malonyl‐1,2‐dihydroisoquinoline chemical delivery systems (CDS). The synthesized N ‐malonyl‐1,2‐dihydroisoquinoline chemical delivery systems were subjected to various chemical and biological investigations to evaluate their ability to cross the blood‐brain barrier (BBB), and to be oxidized biologically into their corresponding quaternary derivatives. The in‐vitro oxidation studies showed that the designed N ‐malonyl‐1,2‐dihydroisoquinoline chemical delivery system could be oxidized into its corresponding quaternary derivatives at an adequate rate. The in‐vivo distribution studies showed that these N ‐malonyl‐1,2‐dihydroisoquinoline chemical delivery systems were able to cross the blood‐brain barrier at detectable concentrations.