ABSTRACT
A series of 23 novel benzylamines was synthesized by reductive amination from halogen-substituted 3- and 4-benzyloxybenzaldehyde derivatives and 6-methylhept-2-yl amine or n-octylamine. The antimycotic activity of the resulting amines was evaluated in a microdilution assay against the apathogenic yeast Yarrowia lipolytica as test microorganism. Promising compounds were also tested against human pathogenic Candida species. The influence of halogen substituents at the benzyl ether side chain was studied in this screening, as well as the influence of the branched side chain of (±)-6-methylhept-2-yl amine in comparison with the n-octyl side chain.
Subject(s)
Antifungal Agents , Benzylamines , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Benzylamines/pharmacology , Benzylamines/chemistry , Benzylamines/chemical synthesis , Structure-Activity Relationship , Candida/drug effects , Molecular Structure , Yarrowia/drug effects , Humans , Dose-Response Relationship, DrugABSTRACT
Benzylamine-type antimycotics like naftifine, butenafine, or terbinafine are a well-known class of antimycotics since the 1980s. The following paper describes the synthesis and biological evaluation of a series of novel benzylamine-type antimycotics characterized by an isooctyl side chain and various substituents at the benzylamine moiety. The compounds were prepared from benzaldehyde derivatives and 2-amino-6-methylheptane by reductive amination with sodium triacetoxyborohydride and subsequent precipitation with hydrogen chloride. The antimycotic activity of the resulting compounds was evaluated in an agar diffusion assay against the yeasts C. glabrata and Yarrowia lipolytica, the mold Aspergillus niger and the dermatophyte H. burtonii. The compounds were also tested in a microdilution assay against the yeast Candida glabrata and the dermatophyte H. burtonii to determine the minimal inhibitory concentrations (MIC). Compounds with an aromatic ether side chain or a short alkyl ether side chain showed significant antimycotic activity against C. glabrata, comparable to terbinafine or clotrimazole.
Subject(s)
Antifungal Agents/pharmacology , Benzylamines/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Aspergillus niger/drug effects , Benzylamines/chemical synthesis , Benzylamines/chemistry , Candida glabrata/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , HL-60 Cells , Humans , Microbial Sensitivity Tests , Molecular Structure , Naphthalenes/chemistry , Naphthalenes/pharmacology , Saccharomycetales/drug effects , Structure-Activity Relationship , Yarrowia/drug effectsABSTRACT
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.
