Inhibitory Activity for Chitin Synthase II from Saccharomyces cerevisiae by Tannins and Related Compounds

Abstract

In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2″-O-galloyl)-β-D-glucoside (6), and kaempferol-3-O-(2″-O-galloyl)-β-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2″-O-galloyl)-β-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-β-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC₅₀ values of 18-206 μM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC₅₀ value of 18 μM. The inhibition appears to be selective for chitin synthase II, as they did not appreciably inhibit chitin synthase III.

Key words

Euphorbia pekinensis - Euphorbiaceae - chitin synthase II - chitin synthase III - chitin synthase II inhibitor - tannins - antifungal agents

References

• 1 Cabib E, Roberts S, Bowers B. Synthesis of the yeast cell wall and its regulation.  Annual Review of Biochemistry. 1982;  51 763-93
• 2 Cabib E, Sburlati A, Bowers B, Silverman S J. Chitin synthase I, an auxiliary enzyme for chitin synthesis in Saccharomyces cerevisiae .  Journal of Cell Biology. 1989;  108 1665-72
• 3 Choi W J, Cabib E. The use of divalent cations and pH for the determination of specific yeast chitin synthases.  Analytical Biochemistry. 1994;  219 368-72
• 4 Hwang E I, Kim Y K, Lee H B, Kim H G, Kim S U. Screening system for chitin synthase II inhibitors from natural resources and its inhibitor prodigiosin.  Journal of Microbiology & Biotechnology. 2000;  10 251-7
• 5 Matsuda H. Studies on the constituents of the leaves of Rhus and of some species of related genera in Japan.  Chemical & Pharmaceutical Bulletin. 1966;  14 877-83
• 6 Nonaka G, Ageta M, Nishioka I. Tannins and related compounds. XXV. A new class of gallotannins possessing a (-)-shikimic acid core from Castanopsis cuspidate var. sieboldii Nakai (1).  Chemical & Pharmaceutical Bulletin. 1985;  3 96-101
• 7 Lee S H, Tanaka K, Nonaka G, Nishiok I, Zhang B. Allose gallates from Euphorbia fischeriana .  Phytochemistry. 1991;  30 1251-3
• 8 Okuda T, Hatano T, Yazaki K. Dehydrogeraniin, furosinin and furosin, dehydroellagi-tannins from Geranium thunbergii .  Chemical & Pharmaceutical Bulletin. 1982;  30 1113-6
• 9 Ishimura K, Nonaka G, Nishioka I. Gallic acid esters of proto-quercitol, quinic acid and (-)-shikimic acid from Quercus mongolica and Q. myrsinaefolia .  Phytochemistry. 1987;  26 1501-4
• 10 Isobe T, Fukushige T, Noda Y. A new flavonoid glycoside from Polygonum nodosum . Chemistry Letters 1979: 27-30
• 11 Chung K T, Lu Z, Chou M W. Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria.  Food & Chemical Toxicology. 1998;  36 1053-60
• 12 Matsuo K, Kobayashi M, Takuno Y, Kuwajima H, Ito H, Yoshida T. Anti-tyrosinase activity constituents of Arctostaphylos uva-ursi .  Yakugaku Zasshi. 1997;  117 1028-32
• 13 Gali H U, Perchellet E M, Klish D S, Johnson J M, Perchellet J P. Antitumor-promoting activities of hydrolysable tannins in mouse skin.  Carcinogenesis. 1992;  13 715-8
• 14 Schiffman S S, Suggs M S, Simon S A. Astringent compounds suppress taste responses in gerbil.  Brain Research. 1992;  595 1-11
• 15 Kim S U, Hwang E I, Nam J Y, Son K H, Bok S H, Kim H E, Kwon B M. Inhibition of chitin synthase II by catechins from stem bark of Taxus cuspidata .  Planta Medica. 1999;  65 97-8
• 16 Jeong T S, Hwang E I, Lee H B, Lee E S, Kim Y K, Bae K H, Bok S H, Kim S U. Chitin synthase II Inhibitory activity of ursolic acid, isolated from Crataegus pinnatifida .  Planta Medica. 1999;  65 261-3