Effect of substituents at phenyl group of 7,7′-dioxo-9,9′-epoxylignane on antifungal activity

Nakazaki

Akiyama

et al. 2017

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The structure-activity relationship of the antifungal fluorinated dihydroguaiaretic acid derivatives was evaluated. Some of the newly synthesized lignan compounds were found to show higher antifungal activity against phytopathogenic fungi such as Alternaria alternata (Japanese pear and apple pathotypes) and A. citri than the lead compound, 3-fluoro-3'-methoxylignan-4'-ol (3). The broad antifungal spectrum of 3'-hydroxyphenyl derivative 16 was observed, and the 3'-fluoro-4'-hydroxyphenyl derivative 38 was found to show the highest activity against the A. alternata Japanese pear pathotype, with an EC value of 11 μM. The preventive effect of the potent lignan on the infection of A. alternata in the Japanese pear's leaves was also shown.

Section: Resultssupporting

confidence: 58%

Structure-Antifungal Activity Relationship of Fluorinated Dihydroguaiaretic Acid Derivatives and Preventive Activity against Alternaria alternata Japanese Pear Pathotype

Nakazaki

Akiyama

et al. 2017

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“…Derivative 5, bearing no substituent on the 7-phenyl group, showed about 2fold higher activity than three stereoisomers. By comparison of derivatives 6−21 bearing one substituent on the phenyl group with derivative 5, the activity of the hydroxyphenyl (6,11,16) and methoxyphenyl (7,12,17) derivatives was 1.5−2.8-fold lower than that of unsubstituted phenyl derivative 5, and the activity of methylphenyl derivatives (8,13,18) was 4-fold lower. On the other hand, the activity of fluorophenyl (9,14,19) and chlorophenyl (10,15,20) derivatives was comparable to or higher than that of phenyl derivative 5.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The cytotoxic lignan, podophyllotoxin, has also been reported as an antifungal lignan. 5 We reported the effect of the stereochemistry of tetrasubstituted tetrahydrofuran lignan, 6 disubstituted tetrahydrofuran lignan, 7 butane type lignan, 8 and sesquineolignan 9 on the antifungal activity. However, quantitative structure− antifungal activity relationship analyses of these lignans have not been done.…”

Section: ■ Introductionmentioning

confidence: 99%

Quantitative Structure–Activity Relationship Analysis of Antifungal (+)-Dihydroguaiaretic Acid Using 7-Phenyl Derivatives

Hasebe

Akiyama

et al. 2013

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The relationship between antifungal activity against Alternaria alternata and structure on the 7-phenyl group of (+)-dihydroguaiaretic acid ((+)-DGA) was clarified by employing 38 synthesized (+)-DGA derivatives. The results were identified by quantitative structure−activity relationship (QSAR) analysis employing the Hansch−Fujita method. Some compounds showed higher activity than (+)-DGA. The compound showing highest activity was 3,5-difluorophenyl derivative 37. It was suggested that the small electron-withdrawing group at the meta-position of the 7-phenyl group is important for the higher activity by antifungal test and Hansch−Fujita analysis. The whitening activity of 3-hydroxy-4-methoxyphenyl derivative 28, 3hydroxy-4-ethoxyphenyl derivative 29, and 3-hydroxy-4-isopropoxyphenyl derivative 30 against A. alternata Japanese pear pathotype was also discovered.

“…For example, antibacterial activity was observed in both 9,9′-epoxylignane (Figure 1, 1−3) and 7,7′dioxo-9,9′-epoxylignane, 4 whereas only 7,7′-dioxo-9,9′-epoxylignane showed antifungal activity. 5 We also reported the effects of the stereochemistry of trisubstituted tetrahydrofuran lignan on plant growth inhibitory activity. 6 On the other hand, dihydroguaiaretic acid (Figure 1, 4−6), whose intramolecular etherification between the 9 and 9′ positions provides 9,9′epoxylignane 1−3, showed larvicidal activity against the mosquitoes Culex pipiens, and some of its derivatives with the substituted benzene ring killed the larvae within 30 min.…”

Section: ■ Introductionmentioning

confidence: 97%

First Discovery of Insecticidal Activity of 9,9′-Epoxylignane and Dihydroguaiaretic Acid against Houseflies and the Structure–Activity Relationship

Wukirsari

Hasebe

et al. 2013

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The insecticidal activity of (-)-(8R,8'R)-3,3'-dimethoxy-9,9'-epoxylignane-4,4'-diol (1) against houseflies was clarified for the first time. The activities of other stereoisomers were weaker than that of the (8R,8'R)-stereoisomer. In the course of research into structure-activity relationships involving 30 newly synthesized (8R,8'R)-derivatives, 5-fold higher activity (ED50 = 0.91 nmol/fly) was observed for (-)-(8R,8'R)-3,3',4-trimethoxy-9,9'-epoxylignan-4'-ol (21) than for the naturally occurring compound (1). The activity of 1 was weaker than that of (-)-(8R,8'R)-dihydroguaiaretic acid ((-)-DGA) (4); however, compound 21 showed almost the same level of activity as 4.