Synthesis and biological evaluation of novel N-alkyl tetra- and decahydroisoquinolines: novel antifungals that target ergosterol biosynthesis

Arch Pharm (Weinheim). 2014 Apr;347(4):283-90. doi: 10.1002/ardp.201300338. Epub 2014 Jan 27.

Abstract

A series of N-alkyl trans-decahydroisoquinoline, 1,2,3,4-tetrahydroisoquinoline, and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized starting from the respective secondary amines by N-alkylation with alkyl bromides. The compounds with C11-alkyl chains showed antifungal potency comparable to clotrimazole, and inhibit enzymes of the ergosterol biosynthesis (Δ14-reductase and Δ8,7-isomerase), depending on the heterocyclic scaffold and the investigated species.

Keywords: Antifungal activity; Enzyme inhibitor; Ergosterol biosynthesis; Δ14-Reductase; Δ8,7-Isomerase.

Publication types

  • Comparative Study

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Clotrimazole / pharmacology
  • Ergosterol / biosynthesis
  • Fungi / drug effects*
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Microbial Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Isoquinolines
  • Clotrimazole
  • Ergosterol