Synthesis and in vitro antifungal activities of new 2-aryl-6,7- methylenedioxy-3, 4-dihydroisoquinolin-2-ium bromides

Abstract

2-Aryl-3,4-dihydroisoquinolin-2-iums might be considered as a class of simple analogues of natural quaternary benzo[c]phenanthridine alkaloids. In this paper, 26 new 2-aryl-6,7-methylenedioxy-3,4-dihydroisoquinolin-2-ium bromides with various substituents in N-aromatic ring were synthesized from commercially available 1,3-benzodioxole in good to excellent yields. All the compounds were elucidated by MS, high resolution (HR)-MS, IR, 1H- and 13C-NMR analysis, and evaluated for antifungal activities in vitro against Alternaria alternate, Curvularia lunata and Fusarium oxysporum sp. niveum at 50 μg/mL. Most of the compounds showed higher activities against all the test fungi than their natural model compounds sanguinarine and chelerythrine. For A. alternate and Curvularia lunata, most of them were also more active than thiabendazole, a commercial fungicide standard. The structure-activity relationship indicated that the substituent in N-aromatic ring and its position had significant effect on the activity. The general trend was that halogen atoms and CF3 remarkably enhanced the activity while CH3 and OCH3 decreased the activity. Generally, o-substituted isomers were more active than m- and p-substituted isomer. The present results suggest that the title compounds are potential for the development of new isoquinoline antimicrobial agents. © 2013 The Pharmaceutical Society of Japan.