# Synthesis and Biological Evaluation of Novel 2‐(Piperidin‐4‐yl)‐1,2,3,4‐tetrahydroisoquinoline and 2‐(Piperidin‐4‐yl)decahydroisoquinoline Antimycotics

## TL;DR

Researchers created 13 new hybrid molecules combining piperidine and isoquinoline structures and tested their antifungal effects against various yeast and mold species.

## Contribution

The paper introduces novel hybrid antimycotic compounds with promising activity against clinically relevant fungal species.

## Key findings

- Five to six compounds showed complete growth inhibition against C. albicans or C. krusei.
- Compound 6i inhibited the growth of aspergilli, and 6k and 6l inhibited Rhizopus arrhizus.
- No antifungal activity was observed against mold isolates, except for specific compounds.

## Abstract

Piperidine antimycotics like fenpropidin are well established in agrochemistry. On the other hand, numerous isoquinoline derivatives show remarkable antimycotic effects. Here we present a series of 13 hybrid molecules of both lead structures, which were prepared using reductive amination as key reaction step. Pre‐screening against Yarrowia lipolytica resulted in a batch of promising candidates whose antifungal efficacy was further evaluated against clinically relevant species. In these assays, complete growth inhibition was seen for five or six compounds against C. albicans or C. krusei, respectively, and in two against C. glabrata, whereas no antifungal activity was observed against mold isolates, with the exception of 6i, which led to complete growth inhibition of aspergilli, and two compounds (6k and 6 l) that were able to inhibit Rhizopus arrhizus.

A series of 13 hybrid molecules of both lead structures were prepared using reductive amination as key reaction step. The antimycotic potency of the resulting compounds was evaluated against yeast and mold species. Two compounds showed remarkable potency against several yeasts, and even against Candida krusei.