Inhibition of Chitin Synthase 2 and Antifungal Activity of Lignans from the Stem Bark of Lindera erythrocarpa

Abstract

Potent chitin synthase 2 inhibitors, methyllinderone (1), linderone (2) and kanakugiol (3) were isolated from the stem bark of L. erythrocarpa Makino (Lauraceae). These compounds inhibited chitin synthase 2 with IC(50) values of 23.3, 21.4 and 23.8 microg/mL, respectively. Methyllinderone (1) and linderone (2) exhibited no inhibitory activities for chitin synthases 1 and 3 from S. cerevisiae, and chitin synthase 1 from Candida albicans up to the concentration of 280 microg/mL, while kanakugiol (3) exhibited very weak activity against chitin synthase 1 of C. albicans with an IC(50) of 160 microg/mL. All of the compounds showed moderate to weak antifungal activities against various pathogenic fungi (MIC: 8 - >128 microg/mL) including Cryptococcus neoformans, Aspergillus fumigatus, and Colletotrichum lagenarium. The results indicate that these compounds are specific inhibitors of chitin synthase 2 and can potentially serve as antifungal agents.

Conformational, electronic and antioxidant properties of lucidone, linderone and methyllinderone: DFT, QTAIM and NBO studies

“…The separation in the IP values for the different structures is also smaller in solution than in vacuo, indicating that, in solution, most compounds have nearly similar tendency to react through ET mechanism. The ET mechanism may offer an explanation for the observation that LD, LR and mLR have the ability to scavenge free radical species, as reported by some experimental researchers [2][3][4][5][6][7][8][9][10]. In all the media, the tendency to scavenge free radicals increases with the increase in the number of OCH 3 groups as substituents on the main moiety, in this way, mLR and LD have the highest and the lowest tendency, respectively, to scavenge free radical species.…”

“…In most part of the world where this plant is found, it is utilised as a traditional medicine for the treatment of several illnesses including analgesic, digestive, diuretic and headache problems [1]. The isolated compounds exhibit several biological activities including antitumor, antiviral, antioxidant, antibacterial, antifungal and antiinflammatory activities, [1][2][3][4][5][6][7][8][9][10][11][12][13]. Therefore, LD, LR and mLR are attractive for utilisation in the therapeutical treatment of degenerative diseases because they are isolated from natural sources and therefore have potential to reduce the risk of drug toxicity [11,12].…”

Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents

“…Enzymes for the construction of the fungal cell wall have been identified as potential molecular targets for chalcones, mainly the (1,3)β- d -glucan synthase and chitin synthase [ 41 , 42 ]. In fact, the chalcones methyllinderone, linderone and kanakugiol ( Figure 4 ), extracted from the stem bark of Lindera erythrocarpa Makino, have shown potent inhibitory activity against chitin synthase 2 (CHS2) from Saccharomyces cerevisiae [ 43 ]. Also, they presented an antifungal activity against C. neoformans comparable to the antifungal activity of the synthesized chalcones here.…”

Anti-inflammatory effect and mechanism of action of Lindera erythrocarpa essential oil in lipopolysaccharide-stimulated RAW264.7 cells

“…They are also used as antidotes and diuretics (Hong et al, 2009[ 13 ]; Oh et al, 2005[ 28 ]; Sun and Chung, 1988[ 35 ]). Recently, L. erythrocarpa was reported to suppress adipogenesis and melanin synthesis, attenuate obesity, as well as exhibit antioxidant, anti-inflammatory, and antifungal activities (Hsieh and Wang, 2013[ 15 ]; Hwang et al, 2007[ 16 ]; Kumar et al, 2010[ 19 ]; Wang et al, 2008[ 40 ]). Essential oils extracted from medicinal and aromatic plants are known to have biological effects, most notably anti-inflammatory, antioxidant, antifungal, and antibacterial activities (Chaieb et al, 2007[ 4 ]; Pinheiro et al, 2011[ 29 ]).…”