Synthesis and biological evaluation of novel N-alkyl tetra- and decahydroisoquinolines: novel antifungals that target ergosterol biosynthesis.
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.
Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University Munich, Munich, Germany.
Jürgen
J
Krauss
Christoph
C
Müller
Julia
J
Kießling
Sabine
S
Richter
Verena
V
Staudacher
Franz
F
Bracher
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003022:Clotrimazole / Q000494:pharmacology; D004875:Ergosterol / Q000096:biosynthesis; D005658:Fungi / Q000187:drug effects*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D007546:Isoquinolines; D003022:Clotrimazole; D004875:Ergosterol
Antifungal activity; Enzyme inhibitor; Ergosterol biosynthesis; Δ14-Reductase; Δ8,7-Isomerase