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

Kinuko Iwasa, Yumi Nishiyama, Momoyo Ichimaru, Masataka Moriyasu, Hye Sook Kim, Yusuke Wataya, Takao Yamori, Turuo Takashi, Dong Ung Lee

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, 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 protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1.

Original languageEnglish
Pages (from-to)1077-1083
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume34
Issue number12
DOIs
Publication statusPublished - Dec 1999

Keywords

  • In vitro antimalarial activity
  • Protoberberinium salts
  • Structure-activity relationships

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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