Molecules 2013, 18(9), 10413-10424; doi:10.3390/molecules180910413
Article

2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

1,†email, 1,†email, 1email, 1email, 2email, 1,* email and 1,* email
Received: 5 July 2013; in revised form: 18 July 2013 / Accepted: 22 August 2013 / Published: 29 August 2013
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Abstract: The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 212 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.
Keywords: 2-aryl-3,4-dihydroisoquinolin-2-ium; antifungal activity; phytopathogenic fungi; structure-activity relationship; sanguinarine; chelerythrine
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MDPI and ACS Style

Hou, Z.; Yang, R.; Zhang, C.; Zhu, L.-F.; Miao, F.; Yang, X.-J.; Zhou, L. 2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships. Molecules 2013, 18, 10413-10424.

AMA Style

Hou Z, Yang R, Zhang C, Zhu L-F, Miao F, Yang X-J, Zhou L. 2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships. Molecules. 2013; 18(9):10413-10424.

Chicago/Turabian Style

Hou, Zhe; Yang, Rui; Zhang, Cen; Zhu, Li-Fei; Miao, Fang; Yang, Xin-Juan; Zhou, Le. 2013. "2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships." Molecules 18, no. 9: 10413-10424.


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