Inhibitors of the fungal cell wall. Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on beta(1-3) glucan and chitin synthases.
As part of our project devoted to the search for antifungal agents, which act via a selective mode of action, we synthesized a series of new 4-aryl- or 4-alkyl-N-arylamine-1-butenes and transformed some of them into 2-substituted 4-methyl-tetrahydroquinolines and quinolines by using a novel three-step synthesis. Results obtained in agar dilution assays have shown that 4-aryl homoallylamines not possessing halogen in their structures, tetrahydroquinolines and quinolines, display a range of antifungal properties in particular against Epidermophyton floccosum and Microsporum canis. Regarding the mode of action, all active compounds showed in vitro inhibitory activities against beta(1-3) glucan-synthase and mainly against chitin-synthase. These enzymes catalyze the synthesis of beta(1-3) glucan and chitin, respectively, major polymers of the fungal cell wall. Since fungal but not mammalian cells are encased in a cell wall, its inhibition may represent a useful mode of action for these antifungal compounds.
Urbina
J M
JM
Laboratory of Fine Organic Chemistry, School of Chemistry, Industrial University of Santander, Bucaramanga, Colombia.
Cortés
J C
JC
Palma
A
A
López
S N
SN
Zacchino
S A
SA
Enriz
R D
RD
Ribas
J C
JC
Kouznetzov
V V
VV
D000499:Allylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects* / Q000201:enzymology; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004821:Epidermophyton / Q000187:drug effects / Q000201:enzymology; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D008864:Microsporum / Q000187:drug effects / Q000201:enzymology; D013057:Spectrum Analysis
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D000499:Allylamine; D006006:Glycogen Synthase; D002687:Chitin Synthase