Synthesis and <i>in Vitro</i> 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, 1 H-and 13 C-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 CF 3 remarkably enhanced the activity while CH 3 and OCH 3 decreased the activity. Generally, osubstituted 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.Key words 3,4-dihydroisoquinolinium; 1,2,3,4-tetrahydroisoquinoline; N-heterocyclization; antifungal activity; CuCl 2 -catalyzed oxidative coupling reaction; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation Alkaloids represent a very extensive group of secondary metabolites with diverse structures, distribution in nature, and biological effects. Natural isoquinolines are one of the largest groups of alkaloids. Among them, there is a relatively small but important class of iminium moiety-containing isoquinoline alkaloids, such as quaternary benzo[c] phenanthridine alkaloids (QBAs), quaternary N-naphthyl isoquinolines, berberines and so on 1,2) (Fig. 1). In the past decades, these compounds have aroused interests of both chemists and pharmacologists for their chemical reactivity and extensive bioactivities including antitumor, [3][4][5] antimicrobial, [6][7][8][9][10][11][12] anti-inflammation, 13) antiplatelet aggregation, 14) anti-angiogenesis, 15) anti-acetylcholinesterase, 16) and antiparasite activities. [17][18][19][20] Our previous studies demonstrated that sanguinarine and chelerythrine ( Fig. 1) might serve as ideal lead compounds to develop new isoquinoline antimicrobial and acaricidal agents. Meanwhile, the iminium moiety (C= N + ) was their determinant for their bioactivities. 11,12,17) The similar cases were also found for antitumor activity of 7-demethyl chelerythrine (NK109) 21) and antibacterial activity of berberine.9) In addition, the molecular planarity was also proven to be an important factor for the activity.21) Based on understanding of the structure-activity relationship above and the aim of developing more potent QBAs-like drugs, we intended to design a cl...

New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships

“…In addition, our study also found that the C=N + moiety in ADHIQs is a determinant for their bioactivities including antifungal properties 5 , 9 , and the antifungal activity of ADHIQs is closely related to the electron density distribution in its conjugated system, especially in the C=N + bond 9 – 13 . The substitution patterns of the two aryl-rings can significantly impact the activity.…”

“…1 ) can be considered as a class of structurally simple analogues of sanguinarine (SA) or chelerythrine (CH) with diverse biological effects, two quaternary benzo[c]phenanthridine alkaloids (QBAs). Our previous study proved that like SA and CH 5 – 8 , ADHIQs generally possessed excellently antifungal 9 – 13 , acaricidal 14 , 15 and anticancer activities 5 , 16 , and also showed high safety to plant growth 17 , 18 . These results show that ADHIQs are of great potential as new or secondary lead compounds to develop QBA-like antifungal agents.…”

Ethyl Cinnamate Derivatives as Promising High-Efficient Acaricides against <i>Psoroptes cuniculi</i>: Synthesis, Bioactivity and Structure–Activity Relationship

“…45) Aromatic aldehyde 1 was obtained from sesamol by the reaction of Vilsmeier-Haack formylation in 11% yield. 46) 1,3-Benzodioxole reacted with paraformaldehyde in a concentrated HCl solution to provide 2, 47) and followed by treatment with bromine in glacial acetic acid to yield 4 in 92% yield. 48) Compounds 2 and 4 were oxidized by dimethylsulphoxide oxidation in the presence of NaHCO 3 to yield intermediates 3 and 5, respectively.…”

Trialkylamine Derivatives Containing a Triazole Moiety as Promising Ergosterol Biosynthesis Inhibitor: Design, Synthesis, and Antifungal Activity

“…[17][18][19] Tebuconazole (≥ 99.1%), a commercial fungicide, was used as the positive control. Compound 7a was regarded as the reference compound.…”