title: 2-(Substituted phenyl)-3,4-dihydroisoquinolin-2-iums as novel antifungal lead compounds: biological evaluation and structure-activity relationships.
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 2-12 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.
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hou
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Cen
authors.initials: C
authors.lastname: Zhang
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Miao
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Yang
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology*; D052978:Disk Diffusion Antimicrobial Tests; D020128:Inhibitory Concentration 50; D003904:Mitosporic Fungi / Q000187:drug effects* / Q000254:growth & development; D010935:Plant Diseases / Q000382:microbiology; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D053119:Benzophenanthridines