Synthesis and Biological Evaluation of Novel N-Alkyl Tetraand 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 C-11-alkyl chains showed antifungal potency comparable to clotrimazole, and inhibit enzymes of the ergosterol biosynthesis (14-reductase and 8,7-isomerase), depending on the heterocyclic scaffold and the investigated species.