Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

Citation
K. Iwasa et al., Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity, EUR J MED C, 34(12), 1999, pp. 1077-1083
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
0223-5234 → ACNP
Volume
34
Issue
12
Year of publication
1999
Pages
1077 - 1083
Database
ISI
SICI code
0223-5234(199912)34:12<1077:SROQPA>2.0.ZU;2-Z
Abstract
Seventeen quaternary protoberberine alkaloids related to berberine I were t ested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protober berine alkaloids was influenced by the type of the oxygen substituents on r ings A, C and D and the position of the oxygen functions on ring D. The pos ition of the oxygen functions on ring D and the type of the oxygen substitu ents at the C-13 position (ring C) strongly influenced the activity. Shifti ng the oxygen functions at C-9 and C-10 to C-10 and C-Il on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedi oxy function at C-2 and C-3 (ring A) or C-9 and C-IO (ring D) showed higher activity than those which have methoxy groups at the same positions. Intro duction of a methoxy group into the C-l position (ring A) decreased the act ivity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy g roup led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, Oft, OCOOEt, and OCON(Me)(2) reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberber ines displayed more potent activity than berberine 1. The activity decrease d in the order: 10, 11, 17 and 18 > 7 and 8 > 1. (C) 1999 Editions scientif iques et medicales Elsevier SAS.