Inhibitors of the Fungal Cell Wall. Synthesis of 4-Aryl-4-N-arylamine-1-butenes and Related Compounds with Inhibitory Activities on (1±3) Glucan and Chitin Synthases

J.URBINA; J.CORTÉS; A.PALMA; S.LOPEZ; S.ZACCHINO; ENRIZ R.D.; J.RIBAS; V. KOUSNETZOV

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2000 vol. 8 p. 691 - 698

0968-0896

As part of our project devoted to the search for antifungal agents, which act via a selective mode of action, we synthe- sized a series of new 4-aryl- or 4-alkyl-N-arylamine-1-butenes and transformed some of them into 2-substituted 4-methyl-tetra- hydroquinolines 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 ¯occosum and Microsporum canis. Regarding the mode of action, all active com- pounds showed in vitro inhibitory activities against b(1±3) glucan-synthase and mainly against chitin-synthase. These enzymes catalyze the synthesis of b(1±3) glucan and chitin, respectively, major polymers of the fungal cell wall. Since fungal but not mam- malian cells are encased in a cell wall, its inhibition may represent a useful mode of action for these antifungal compounds