LIPIDIC PEPTIDES .2. SYNTHESIS, ACTIVITY AND TRANSPORT OF ANTIINFLAMMATORY BENZOQUINOLIZINE-LIPIDIC PEPTIDE CONJUGATES

被引：17

作者：

TOTH, I ^{[1
]}

HUGHES, RA ^{[1
]}

MUNDAY, MR ^{[1
]}

MURPHY, CA ^{[1
]}

MASCAGNI, P ^{[1
]}

GIBBONS, WA ^{[1
]}

机构：

[1] UNIV LONDON,SCH PHARM,29-39 BRUNSWICK SQ,LONDON WC1N 1AX,ENGLAND

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 1991年 / 68卷 / 1-3期

关键词：

LIPIDIC AMINO ACID; LIPIDIC PEPTIDE; TRANSMEMBRANE DRUG DELIVERY; ANTIINFLAMMATORY DRUG; ORAL ABSORPTION; HISTAMINE RELEASE;

D O I：

10.1016/0378-5173(91)90141-A

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Two series of lipidic peptide conjugates 1c-1i and 2c-2e of the anti-inflammatory benzoquinolizine alkaloids 1b and 2b were synthesised. The biological activities of the conjugates 1c, 1d and 1f were assessed by determining their ability to inhibit the release of histamine from rat mast cells in vitro. Conjugates 1d and 1f, their parent alkaloid 1b and its methyl ester 1a, gave 40-50% inhibition, whereas conjugate 1c showed 2-fold greater activity. The radiolabelled compounds 2a* and 2c* were produced by reduction of 1a and 1f with NaB3H4. Following their oral administration to rats, peak serum levels of the conjugate 2c* were 5 times greater than that observed for the parent compound 2a*. The results suggest that conjugation to lipidic amino acids and peptides can be a useful approach to improving the oral absorption of poorly absorbed drugs.

引用

页码：191 / 198

页数：8