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

Abstract

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 EC 50 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

Synthesis and <i>in Vitro</i> Antifungal Activities of Novel Benzamide Derivatives Containing a Triazole Moiety

“…1,3,[10][11][12] Compound 5, 1-amino-3,3-dimethyl-2-(1H-1,2,4-triazol-1-yl) methyl-2-butanol, a key intermediate, was regarded as the reference compound, whose antifungal activity was also assayed by the same methodology, and myclobutanil, a commercial fungicide, was used as the positive control. The results are displayed in Table 1.…”

“…The assay method was the same as that mentioned above. 1,3,11,13) Compound 5 and myclobutanil were used as the reference compound and positive control, respectively. Toxicity regression equations for concentration-effect of the compounds and their corresponding EC 50 values are listed in Tables 2 to 6.…”

“…IR (KBr) cm 1,3,10,11,13) with minor modification. The test fungi, provided by the Center of Pesticide Research, Northwest A&F University, China, and maintained on potato dextrose agar (PDA) medium slants were subcultured for 48 h in Petri dishes prior to testing and used for inoculation of fungal strains on PDA plates.…”

“…1) These fungi can invade all the tissues of a plant at its any growth stage, thereby leading to significant losses in the yield and quality of agricultural products. [1][2][3] Moreover, many fungal plant pathogens could produce mycotoxins, the fungal secondary metabolic products that may pose a threat to animal and human health. 1,3,4) Therefore, the effective control of fungal diseases is extremely essential for agricultural production, food safety and human health worldwide.…”

“…[1][2][3] Moreover, many fungal plant pathogens could produce mycotoxins, the fungal secondary metabolic products that may pose a threat to animal and human health. 1,3,4) Therefore, the effective control of fungal diseases is extremely essential for agricultural production, food safety and human health worldwide. 2,3) To date, chemical control is still considered as an efficient measure for preventing and controlling these diseases, 2) and various synthesized fungicides have been extensively developed and commercially available.…”