Synthesis and Antifungal Evaluation of Novel N-Alkyl Tetra- and Perhydroquinoline Derivatives.

Jürgen Krauß

doi:10.3797/scipharm.1409-13

Abstract

A series of novel N-alkyl tetra- and perhydroquinoline derivatives and their hydrochlorides were prepared from tetrahydro- or trans-perhydroquinoline by direct alkylation with alkyl halides and subsequent precipitation with HCl gas. The antimicrobial activity of the resulting amines was evaluated in an agar diffusion assay. The minimal inhibitory concentrations (MIC) of the active compounds were determined by the microdilution method. In contrast to the tetrahydroquinolines, the perhydro analogues showed significant antifungal activity. In an assay for the detection of target enzymes in ergosterol biosynthesis, N-undecylperhydroquinoline was identified as an inhibitor of Δ8,7-isomerase.

Highlights

In the last few decades, a dramatic increase in fungal infections was observed in the Northern Hemisphere
In continuation of our above-mentioned work [8, 9], we evaluated the antifungal potency of simple N-alkyl tetrahydro- and perhydroquinoline derivatives in the present work
The amines were dissolved in dry diethyl ether and precipitated with HCl gas to give the more stable hydrochlorides 3a–d

Summary

Introduction

In the last few decades, a dramatic increase in fungal infections was observed in the Northern Hemisphere. Cancer patients, organ-engrafted patients, and immunecompromised patients (e.g. AIDS patients) are predisposed to systemic fungal infections by Candida or Aspergillus species with a high lethality. A few drugs from three classes can be used in the treatment of these life-threatening systemic infections: azoles (e.g. fluconazole, posaconazole, or voriconazole), polyene macrolides (e.g. amphotericin B), and echinocandins (e.g. caspofungin, anidulafungin, or micafungin) [1, 2] (Fig. 1). J. Krauß et al.: OH N O OH OH N F HO N N OH N F O OH OH OH OH O O

Methods

Results

Conclusion