Constituents of Cinnamon Inhibit Bacterial Acetyl CoA Carboxylase

Glen Meades; Rachel L. Henken; Grover L. Waldrop; Md. Mukhlesur Rahman; S. Douglass Gilman; Guy P. P. Kamatou; Alvaro M. Viljoen; Simon Gibbons

doi:10.1055/s-0030-1249778

Planta Medica, Inhaltsverzeichnis

Planta Med 2010; 76(14): 1570-1575
DOI: 10.1055/s-0030-1249778

Pharmacology

Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Constituents of Cinnamon Inhibit Bacterial Acetyl CoA Carboxylase

Glen Meades¹ Jr. , Rachel L. Henken² , Grover L. Waldrop¹ , Md. Mukhlesur Rahman³ , S. Douglass Gilman² , Guy P. P. Kamatou⁴ , Alvaro M. Viljoen⁴ , Simon Gibbons³

¹Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, Louisiana, USA
²Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, USA
³Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, London, UK
⁴Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa

Abstract

Cinnamon bark (Cinnamomum zeylanicum) is used extensively as an antimicrobial material and currently is being increasingly used in Europe by people with type II diabetes to control their glucose levels. In this paper we describe the action of cinnamon oil, its major component, trans-cinnamaldehyde, and an analogue, 4-hydroxy-3-methoxy-trans-cinnamaldehyde against bacterial acetyl-CoA carboxylase in an attempt to elucidate the mechanism of action of this well-known antimicrobial material. These natural products inhibited the carboxyltransferase component of Escherichia coli acetyl-CoA carboxylase but had no effect on the activity of the biotin carboxylase component. The inhibition patterns indicated that these products bound to the biotin binding site of carboxyltransferase with trans-cinnamaldehyde having a K_i value of 3.8 ± 0.6 mM. The inhibition of carboxyltransferase by 4-hydroxy-3-methoxy-trans-cinnamaldehyde was analyzed with a new assay for this enzyme based on capillary electrophoresis. These results explain, in part, the antibacterial activity of this well-known antimicrobial material.

Key words

Cinnamomum zeylanicum - Lauraceae - trans‐cinnamaldehyde - acetyl‐CoA carboxylase - carboxyltransferase

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References

1 The King James Bible, Exodus, 30: 23 – 26.
2 Farrell K T. Spices, condiments and seasonings. New York; The AVI Publisher Co. 1985
3 Mishra A, Bhatti R, Singh A, Ishar M P S. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy. Planta Med. 2010; 76 412-417
4 de Luis D A, Aller R, Romero E. Cinnamon as possible treatment of diabetes mellitus type 2. Med Clin (Barc). 2008; 131 279
5 Ammon H P. Cinnamon in type 2 diabetics. Med Monatsschr Pharm. 2008; 31 179-183
6 Baker W L, Gutierrez-Williams G, White C M, Kluger J, Coleman C I. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care. 2008; 31 41-43
7 Dugoua J J, Seely D, Perri D, Cooley K, Forelli T, Mills E, Koren G. From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark. Can J Physiol Pharmacol. 2007; 85 837-847
8 Suppapitiporn S, Kanpaksi N, Suppapitiporn S. The effect of cinnamon cassia powder in type 2 diabetes mellitus. J Med Assoc Thai. 2006; 89 (Suppl. 3) S200-S205
9 Inouye S, Uchida K, Nishiyama Y, Hasumi Y, Yamaguchi H, Abe S. Combined effect of heat, essential oils and salt on fungicidal activity against Trichophyton mentagrophytes in a foot bath. Nippon Ishinkin Gakkai Zasshi. 2007; 48 27-36
10 Pozzatti P, Scheid L A, Spader T B, Atayde M L, Santurio J M, Alves S H. In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp. Can J Microbiol. 2008; 54 950-956
11 Prabuseenivasan S, Jayakumar M, Ignacimuthu S. In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med. 2006; 6 39
12 Shahverdi A R, Monsef-Esfahani H R, Tavasoli F, Zaheri A, Mirjani R. trans-Cinnamaldehyde from Cinnamomum zeylanicum bark essential oil reduces the clindamycin resistance of Clostridium difficile in vitro. J Food Sci. 2007; 72 S055-S058
13 Wong S Y, Grant I R, Friedman M, Elliott C T, Situ C. Antibacterial activities of naturally occurring compounds against Mycobacterium avium subsp. paratuberculosis. Appl Environ Microbiol. 2008; 74 5986-5990
14 Mosqueda-Melgar J, Raybaudi-Massilia R M, Martín-Belloso O. Combination of high-intensity pulsed electric fields with natural antimicrobials to inactivate pathogenic microorganisms and extend the shelf-life of melon and watermelon juices. Food Microbiol. 2008; 25 479-491
15 Marongiu B, Piras A, Porcedda S, Tuveri E, Sanjust E, Meli M, Sollai F, Zucca P, Rescigno A. Supercritical CO₂ extract of Cinnamomum zeylanicum: chemical characterization and antityrosinase activity. J Agric Food Chem. 2007; 55 10022-10027
16 Kim D H, Kim C H, Kim M S, Kim J Y, Jung K J, Chung J H, An W G, Lee J W, Yu B P, Chung H Y. Suppression of age-related inflammatory NF-kappaB activation by cinnamaldehyde. Biogerontology. 2007; 8 545-554
17 McCarty M F. Toward prevention of Alzheimers disease – potential nutraceutical strategies for suppressing the production of amyloid beta peptides. Med Hypotheses. 2006; 67 682-697
18 Kannappan S, Jayaraman T, Rajasekar P, Ravichandran M K, Anuradha C V. Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singapore Med J. 2006; 47 858-863
19 O'Keefe J H, Gheewala N M, O'Keefe J O. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol. 2008; 51 249-255
20 Qin B, Polansky M M, Sato Y, Adeli K, Anderson R A. Cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals. J Nutr Biochem. 2009; 20 901-908
21 Gibbons S, Udo E E. The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet(K) determinant. Phytother Res. 2000; 14 139-140
22 Ross J I, Farrell A M, Eady E A, Cove J H, Cunliffe W J. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis. J Antimicrob Chemother. 1989; 24 851-862
23 Richardson J F, Reith S. Characterization of a strain of methicillin-resistant Staphylococcus aureus (EMRSA-15) by conventional and molecular methods. J Hosp Infect. 1993; 25 45-52
24 Kaatz G W, Seo S M, Ruble C A. Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1993; 37 1086-1094
25 Blanchard C Z, Lee Y M, Frantom P A, Waldrop G L. Mutations at four active site residues of biotin carboxylase abolish substrate-induced synergism by biotin. Biochemistry. 1999; 38 3393-3400
26 Blanchard C Z, Waldrop G L. Overexpression and kinetic characterization of the carboxyltransferase component of acetyl-CoA carboxylase. J Biol Chem. 1998; 273 19140-19145
27 Cleland W W. Statistical analysis of enzyme kinetic data. Methods Enzymol. 1979; 63 103-138
28 Cronan J E, Waldrop G L. Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res. 2002; 41 407-435
29 Levert K L, Waldrop G L. A bisubstrate analog inhibitor of the carboxyltransferase component of acetyl-CoA carboxylase. Biochem Biophys Res Commun. 2002; 291 1213-1217
30 Glatz Z. Determination of enzymatic activity by capillary electrophoresis. J Chromatogr B. 2006; 841 23-37
31 Chantiwas R, Yan X, Gilman S D. Biological applications of microfluidics. Hoboken; John Wiley & Sons 2008: 135-170
32 Holden H M, Benning M M, Haller T, Gerlt J A. The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme A thioesters. Acc Chem Res. 2001; 34 145-157
33 Hamed R B, Batchelar E T, Clifton I J, Schofield C J. Mechanisms and structures of crotonase superfamily enzymes – how nature controls enolate and oxyanion reactivity. Cell Mol Life Sci. 2008; 65 2507-2527
34 Bilder P, Lightle S, Bainbridge G, Ohren J, Finzel B, Sun F, Holley S, Al-Kassim L, Spessard C, Melnick M, Newcomer M, Waldrop G L. The structure of the carboxyltransferase component of acetyl-CoA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme. Biochemistry. 2006; 45 1712-1722
35 Leonard P M, Brzozowski A M, Lebedev A, Marshall C M, Smith D J, Verma C S, Walton N J, Grogan G. The 1.8 Å resolution structure of hydroxycinnamoyl-coenzyme A hydratase-lyase (HCHL) from Pseudomonas fluorescens, an enzyme that catalyses the transformation of feruloyl-coenzyme A to vanillin. Acta Crystalllogr D. 2006; D62 1494-1501
36 Bahnson B J, Anderson V E, Petsko G A. Structural mechanism of enoyl-CoA hydratase: Three atoms from single water are added in either an E1cb stepwise or concerted fashion. Biochemistry. 2002; 41 2621-2629
37 Miller J R, Dunham S, Mochalkin I, Banotai C, Bowman M, Buist S, Dunkle B, Hanna D, Harwood H J, Huband M D, Karnovsky A, Kuhn M, Limberakis C, Liu J Y, Mehrens S, Mueller W T, Narasimhan L, Ogden A, Ohren J, Prasad J V N V, Shelly J A, Skerlos L, Sulavik M, Thomas V H, VanderRoest S, Wang L, Wang Z, Whitton A, Zhu T, Stover C K. A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore. PNAS. 2009; 106 1737-1742
38 Freiberg C, Brunner N A, Schiffer G, Lampe T, Pohlmann J, Brands M, Raabe M, Häbich D, Ziegelbauer K J. Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity. J Biol Chem. 2004; 279 26066-26073
39 Congreve M, Chessari G, Tisi D, Woodhead A J. Recent developments in fragment-based drug discovery. J Med Chem. 2008; 51 3661-3680

Simon Gibbons

Department of Pharmaceutical and Biological Chemistry
The School of Pharmacy
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