Scholarly article on topic 'Antifungal activities of amino acid ester functional pyrazolyl compounds against Fusarium oxysporum f.sp. albedinis and Saccharomyces cerevisiae yeast'

Antifungal activities of amino acid ester functional pyrazolyl compounds against Fusarium oxysporum f.sp. albedinis and Saccharomyces cerevisiae yeast Academic research paper on "Chemical sciences"

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{"Multidentate ligands" / Pyrazole / "Amino acid ester hydrochlorides" / "Antifungal activities"}

Abstract of research paper on Chemical sciences, author of scientific article — Nouria Boussalah, Rachid Touzani, Faiza Souna, Iman Himri, Mohammed Bouakka, et al.

Abstract Series of functional multidendate ligands based on pyrazole and amino acid derivatives were prepared in good and excellent yields (75–5%) by condensation of one equivalent of amino acid ester hydrochloride substrates with two equivalents of (3,5-dimethyl-1H–pyrazol-1-yl)methanol. These tridentate functionalized compounds and their starting materials were screened for their antifungal activities against Fusarium oxysporum f.sp. albedinis and the yeast of Saccharomyces cerevisiae. Considerable activities were recorded with respect to the two studied microorganisms.

Academic research paper on topic "Antifungal activities of amino acid ester functional pyrazolyl compounds against Fusarium oxysporum f.sp. albedinis and Saccharomyces cerevisiae yeast"

Journal of Saudi Chemical Society (2013) 17, 17-21

ORIGINAL ARTICLE

Antifungal activities of amino acid ester functional pyrazolyl compounds against Fusarium oxysporum f.sp. albedinis and Saccharomyces cerevisiae yeast

Nouria Boussalah a, Rachid Touzani b'c, Faiza Souna d, Iman Himri d, Mohammed Bouakka d, Abdelkader Hakkou d'*, Said Ghalem a, Sghir El Kadiri b

a Laboratoire des Substances Naturelles et Bioactives, Département de Chimie, Faculté des Sciences, Université Abou Bekr Belkaid-Tlemcen, BP: 119, Tlemcen 13000, Algeria

b Laboratoire de Chimie Appliqme et Environnement, URAC18, Faculte des Sciences, Universite Mohamed 1er, BP: 524, 60000 Oujda, Morocco

c Faculte Pluridisciplinaire de Nador, BP:300, Selouane 62700, Nador, Morocco

d Laboratoire de Biochimie, Departement de Biologie, Faculte des Sciences, Universite Mohamed 1er, BP:524, 60000 Oujda, Morocco

Received 21 May 2010; accepted 21 February 2011 Available online 24 February 2011

KEYWORDS

Multidentate ligands; Pyrazole; Amino acid ester hydrochlorides; Antifungal activities

Abstract Series of functional multidendate ligands based on pyrazole and amino acid derivatives were prepared in good and excellent yields (75-5%) by condensation of one equivalent of amino acid ester hydrochloride substrates with two equivalents of (3,5-dimethyl-1H-pyrazol-1-yl)metha-nol. These tridentate functionalized compounds and their starting materials were screened for their antifungal activities against Fusarium oxysporum f.sp. albedinis and the yeast of Saccharomyces cerevisiae. Considerable activities were recorded with respect to the two studied microorganisms.

© 2011 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

* Corresponding author. Tel.: +212 0536531414; fax: +212 0536531919.

E-mail address: kadahakkou@yahoo.fr (A. Hakkou).

1319-6103 © 2011 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

Peer review under responsibility of King Saud University. doi:10.1016/j.jscs.2011.02.016

1. Introduction

The discovery of new efficacious antifungal agents is one of humanity's most vital tasks. It is an enormously demanding activity that requires a vast range of scientific knowledge and great persistence. These encourage researchers to discover, develop and synthesize new efficient, active and less toxic molecules for systemic activities (Johnson and Li, 2007; Tan et al., 2004). Concerning the agricultural area, Fusarium oxysporum species are one of the most important fungal organisms of cultivated soils (Jaiti et al., 2008; Yahyi et al., 2007; El Modafar et al., 2006; Bouizgarne et al., 2006). It constitutes, just alone, 40-70% of the total fusariosis flora. It

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was represented with an ensemble of variable forms in terms of morphologic and physiologic views. The behaviors of these forms appear as saprophytes as well as parasites in different plants. Among the last forms, different rates of virulence can be presented. The number of pathogen forms of F. oxysporum is estimated at 80 forms, some of them were capable of producing a plant disease for more than one plant family such as F. oxysporum f.sp. apii (Lori et al., 2008; Pantelides et al., 2009; Paparu et al., 2008; Thangavelu et al., 2004; Fravel et al., 2003) which attacks celery and pea, F. oxysporum f.sp. vasinfectum (Schenk et al., 2009; Alabouvette et al., 2009; De Waele and Elsen, 2007; Pedras and Ahiahonu, 2005; Sharma et al., 2001) which attacks cotton, tobacco and alfalfa, F. oxysporum f.sp. lycopersici (Govindappa et al., 2010; Alexander et al., 2009; Cummings et al., 2009; Van Der Does and Rep, 2007; Haas and Defago, 2005) which attacks tomatoes and F. oxysporum f.sp. melonis which attacks melon. The F. oxysporum f.sp. albedinis (Bautista-Barios et al., 2006; Daboussi and Capy, 2003; Armengol et al., 2005; Weller et al., 2002; Gordon and Martyn, 1997) and the F. oxysporum f.sp. cubense (Weyens et al., 2009; Stukenbrock and McDonald, 2008; Fierro and Martin, 1999; McDonald and Linde, 2002; Lodewyckx et al., 2002; Al Bay et al., 2010; El Kodadi et al., 2007; Waring et al., 2002) which are causal agents of the vascular fusariosis wilt (Bayoud: it is another word for F. oxysporum f.sp. albedinis but it is known in Morocco as Bayoud) of the palm tree and the fusariose of banana tree, respectively, represent the two most serious diseases. Regarding

the antifungal activities, we report our contribution to this subject by testing new synthetic molecules and their precursors (Scheme 1) for toxicity against the growth of two microorganisms: F. oxysporum f.sp. albedinis and the budding yeast Saccharomyces cerevisiae yeast (Rawsthorne and Phister, 2009; Cebollero and Reggiori, 2009; Robinson and Erasmus, 2009; Tamaki, 2007; Bowers and Stevens, 2005).

2. Experimental

2.1. Apparatus

The 1H NMR spectra and 13C NMR spectra were recorded on a Bruker 300 (operating at 300.13 MHz for 1H, 75.47 MHz for 13C in CDCl3) spectrometer. Chemical shifts were listed in ppm and were reported relative to tetramethylsilane. The IR spectra were taken using KBr discs on Mattson Genisis FTIR. The mass spectra have been obtained on a Micromass LCT.

2.2. General method for synthesis of ligands

Diethylisopropylamine (1.96 g, 17 mmol) was added to the suspension of the amine ester hydrochloride (15 mmol) in 40 mL of anhydrous DMF or CH3CN. The mixture was stirred under nitrogen for 5 min and a solution of (3,5-dimethyl-1H-pyrazol-1-yl)methanol (3.8 g, 30 mmol) in anhydrous DMF or CH3CN (50 mL) was added dropwise. The reaction was allowed to stir from four to six days under nitrogen atmosphere. The mixture

was dissolved in 30 mL of water and the compound was extracted by diethyl ether. The organic layers were washed with saturated brine solution, dried over Na2SO4, filtered and concentrated to yield the oils which were put in vacuum desiccators.

2.3. Characteristic of methyl 2-(bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amino)-3-(1H-indol-3-yl)propanoate: P7

Orange oil; yield = 75%; 1H NMR (CDCl3): 1.99 (s, 6H, CH3-Pz); 2.21 (s, 6H, CH3-Pz); 3.10-3.17 (dd, 1H, J = 6.92 Hz, —C21H); 3.32-3.39 (dd, 1H, J = 6.62 Hz, -C21H); 3.51 (s, 3H, -OCH3); 4.13 (t, 1H, J= 7.38 Hz, -C22H); 5.07-5.20 (two doublets, 4H, J = 13.64 Hz, C(1)H(a), C(12)H(a), C(1)H(b), C(12)H(b)); 5.77 (s, 2H, -C4H); 6.69 (d, 1H, J= 2.20 Hz, -C13H); 7.06 (t, 1H, J = 7.02 Hz -C17H); 7.15 (t, 1H, J = 6.98 Hz, -C18H) ; 7.29 (d, 1H,J = 8.15 Hz, -C16H); 7.42 (d, 1H, J = 7.98 Hz, -C19H); 8.39 (s, 1H, -NH). 13C NMR (CDCl3): 173.12 (C23); 146.97 (C5 and C7; C-CH3); 139.65 (C2 and C10; C-CH3); 136.76; 128.12; 118.9; 120.18; 122.67; 112.34 (C20, C15, C16, C17, C18 and C19); 123.76(C13); 109.87(c14); 105.94 (C4 and C9; CH-Pz); 71.48 (C22); 61.52 (C1 and C12; N-CH2-N); 51.97 (C24; O-CH3); 24.70 (C21); 13.55 (C6 and C8; C-CH3); 10.59 (C3-C11;C-CH3). IR (KBr, cm—1): 3052-2918 (vC-H); 1731 (vC=O); 1666-1458 (vC=N, C= C); 1379;1304; 1194 (vC-O);1171; 1114 (vC-N); 1109; 1063; 1031; 979; 797 (dC-H); 742. MS (Electro spray): 434.48 (100%); 338.56 (50%); 326.61 (65%); 230.85 (40%); 213.59 (95%); 192.55 (30%); 181.84 (25%); 101.91(15%).

3. Results and discussion

3.1. Chemistry

New functional pyrazolyl derivatives P1-P7 were prepared, respectively, by condensation of two equivalents of (3,5-di-methyl-1 H-pyrazol-1-yl)methanol 1 (Dvoretzky and Richter, 1950; Touzani et al., 2003; Touzani et al., 2001; Garbacia et al., 2005; Bouabdallah et al., 2007; El Kodadi et al., 2008; Touzani et al., 2011) with one equivalent of amino acid ester hydrochloride derivatives E1-E7 (commercially available) in anhydrous solvents. All reactions were carried out at room temperature under stirring for 4 to 6 days and under inert atmosphere. The compounds from P1 to P6 were already described and published (Boussalah et al., 2009) whereas P7 is a new one (Scheme 1). The proton NMR spectrum for P7 was similar with that reported in the literature (Scarpellini et al., 2005; Roh et al., 2001; Spadoni et al., 1992; Zumbuehl et al., 2009; Manriquez et al., 2009).

3.2. Antifungal activities

The activities of the compounds E1-E7 and P1-P7 were determined by the agar techniques (Carrod and Grady, 1972). The yeast ofS. cerevisiae was realized in a Sabouraud solid medium mixture (2% of glucose, 1% pentane type I and 2% agar-agar) whereas, the F. oxysporum f.sp. albedinis which was isolated from a date palm which was touched by the vascular Fusarium prepared in PDA (potato dextrose agar) medium at 37 g/L. The agar media were incubated (at 28 0C) with the microorganisms and a solution of the tested compound in DMSO/

EtOH (50/50) and then added to different concentration in the culture media. The growth is followed by counting of cell lines for yeasts and by a measure of the diameter of the mecy-lium for Fusarium. The percentage of inhibition of a molecule is equal to the report of the number of cell lines or the diameter of the mycelium of the culture in the presence of a dose of the tested compound on the number of colony or the diameter of the mycelium of the culture witness multiplied by 100. The minimum inhibitory concentration (MIC) is the lowest concentration of antimicrobial agent which inhibits the growth of the microorganism. The determination of the MIC involves a semi-quantitative test procedure which gives an approximation to the lowest concentration of an antimicrobial needed to prevent microbial growth. In the recent past, the method used tubes of growth broth containing a test level of preservative, into which an inoculum of microbes was added. The end result of the test was the minimum concentration of antimicrobial which gave a clear solution, i.e., no visual growth. The various tested compounds show different inhibition actions against the two studied microorganisms' growth. The degree of this inhibition varies from a microorganism to another. In Tables 1 and 2 we report the rate of the inhibition of the growth ofS. cerevisiae yeast (expressed in percentages compared with the blank culture), in different concentrations from 0 to 480 mg/L for the amino acid ester hydrochlorides or their tripodal pyrazolic homologs.

In Tables 3 and 4 we report the rates of the inhibition of the growth of F. oxysporum f.sp. albedinis (expressed in percentages compared with the blank culture), in different concentrations from 0 to 480 mg/L for the amino acid ester hydrochlorides or their tripodal pyrazolic homologs.

The different tested compounds, except P1 and P2, showed an inhibition action against the growth of the funguses: S. cerevisiae yeast and F. oxysporum f.sp. albedinis. However, the rate of this inhibition changes from one molecule to another and from one microorgranism to another. The amino acid ester tryptophane E7 bearing an aromatic indol moiety was very efficient for inhibiting the growth of S. serevisiae yeast with an estimated MIC equal to 8 mg/L followed by va-line, leucine, alanine and phenylalanine with variable MIC between 20 and 24 mg/L. Whereas the glycocoll amino acid ester hydrochlorides E1 and E2 which do not have a substituted asymmetric group, showed a weak inhibition action against S. cerevisiae yeast with MIC from 60 to 50 mg/L, respectively (Table 1). By comparing the amino acid ester hydrochlorides starting materials to their tridentate homologs, we can conclude :

(i) A big increase in the tryptophane ester P7 and the phen-ylalanine ester P3, which is actually a 2.5-fold difference in MIC (25 vs 10).

(ii) An increase in the alanine ester P5 with MIC equal to 7 mg/L and for valine ester P6 and leucine ester P7 with MIC equal to15 mg/L, with a twofold difference (7 vs 15).

(iii) A complete decrease for glycine ester P1 and P2 derivatives, without any antifungal activities (Tables 2 and 4).

(iv) The first series were characterized by bearing an aromatic chain group and the second were characterized by a hydrophobic carbon chain group, whereas no chain was borne by the third series (Table 2).

Table 1 Rate of the inhibition of the growth of Saccharomyces cerevisiae according to the concentration of the commercial compounds E1-E7.

Product Concentration (mg/L) MIC (mg/L)

00.0 06.0 12.0 18.0 24.0 30.0 60.0 120.0 240.0 480.0

E1 00.0 00.0 00.0 00.0 00.0 00.0 00.0 10.1 16.6 45.7 60.0

E2 00.0 00.0 00.0 00.0 00.00. 00.0 05.2 12.4 20.2 37.9 50.0

E3 00.0 00.0 00.0 00.0 00.0 03.5 15.0 23.4 39.4 87.3 24.0

E4 00.0 00.0 00.0 00.0 04.5 09.7 12.7 30.3 47.8 60.3 22.0

E5 00.0 00.0 00.0 00.0 00.0 13.4 45.3 64.8 82.7 100.0 24.0

E6 00.0 00.0 00.0 00.0 10.4 13.3 22.5 63.8 100.0 100.0 20.0

E7 00.0 00.0 24.5 55.7 73.4 90.8 100.0 100.0 100.0 100.0 08.0

Table 2 Rate of the inhibition of the growth of Saccharomyces cerevisiae according to the concentration of the synthesized compounds P1-P7.

Product Concentration (mg/L) MIC (mg/L)

00.0 05.0 10.0 15.0 20.0 25.0 50.0 100.0 250.0 500.0

P1 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00 0 -

P2 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00 0 -

P3 00.0 00.0 00.0 00.0 00.0 00.0 10.2 34.4 59.9 77 6 25 0

P4 00.0 00.0 00.0 00.0 03.3 07.7 33.9 67.9 90.5 100 0 15 0

P5 00.0 00.0 06.7 13.8 25.0 43.4 45.1 64.3 67.7 96 3 07 0

P6 00.0 00.0 00.0 00.0 05.1 10.5 18.9 24.9 77.6 91 5 15 0

P7 00.0 00.0 00.0 03.9 11.7 34.7 39.0 57.3 57.3 62 8 10 0

Table 3 Rate of the inhibition of the growth of Fusarium oxysporum f.sp. albedinis according to the concentration of the commercial compounds E1-E7.

Product Concentration (mg/L) MIC (mg/L)

00 0 06 0 12 0 18 0 24 0 30 .0 60.0 120.0 240.0 480.0

E1 00 0 00 0 00 0 00 0 00 0 02 .1 03.4 11. 36.6 55.7 28.0

E2 00 0 00 0 00 0 00 0 00 0 05.6 10.2 1 30.2 47.9 27.0

E3 00 0 00 0 00 0 00 0 03 7 10.5 55.8 19. 79.4 85.9 18.0

E4 00 0 00 0 00 0 00 0 04 5 09.7 12.7 4 47.8 60.3 22.0

E5 00 0 00 0 00 0 00 0 14 3 23.4 55.7 73. 80.3 97.9 20.0

E6 00 0 00 0 00 0 00 0 10 4 17.3 42.5 3 90.7 100.0 20.0

E7 00 0 03 0 37 2 65 7 85 4 100.0 100.0 100.0 100.0 100.0 03.0

Table 4 Rate of the inhibition of the growth of Fusarium oxysporum f.sp. albedinis according to the concentration of the synthesized compounds P1-P7.

Product Concentration (mg/L) MIC (mg/L)

00.0 05.0 10.0 15.0 20.0 25.0 50.0 100.0 250.0 500.0

P1 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 -

P2 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 00.0 -

P3 00.0 00.0 00.0 00.0 04.8 07.9 11.9 24.7 69.9 94.7 17.0

P4 00.0 00.0 00.0 00.0 04.8 17.7 33.9 77.9 100.0 100.0 15.0

P5 00.0 03.3 09.8 15.8 27.0 33.8 45.5 54.9 62.9 66.0 03.0

P6 00.0 00.0 00.0 05.6 11.1 10.7 13.7 24.9 57.6 72.3 10.0

P7 00.0 00.0 02.7 13.7 20.7 24.7 29.0 49.5 57.9 66.7 05.0

(v) The presence of asymmetric carbon in the backbones of the tested products P3-P7 may be necessary in the inhibition of the growth of the two microorganisms.

The amino acid ester hydrochlorides and their bipyrazolic homolog compounds have shown an effect on the growth of

the F. oxysporum f.sp. albedinis similar to those observed on the yeast with a weak MIC (Tables 3 and 4). This shows that these products were very efficient against the Fusarium. Under the non protonic form, the amino acid ester derivatives traversed the cell membrane via simple permeation and were caught via protonation and hydrolyzed in the lysosome. These

compounds have a behavior like that of activated prodrugs via the proteases lysosomics of the cell (Chauviere-Ramazeilles, 1990). The accumulation of amino acids which were liberated can lead to the osmotic lysis of principal organelles such as the lysosomes of eukaryote cells similar to the yeast. The difference between action of the amino acid esters hydrochloride and their bipyrazoles homologs against the two microorganisms may be explicated by the rate of permeation of these compounds via the cell envelope and or their affinities for the lysosomal proteases. The mechanism of this remarkable process has yet to be determined, but we do not have enough evidence to suggest an intriguing reaction pathway. In conclusion, we have tested antifungal activities of a new variety of tripodal pyrazole functional compounds and their amino acid esters hydrochloride starting materials against yeast cells of S. cere-visiae and Fusarium f.sp. oxysporum Albedinis. The structural and the electronic diversity of these products affected their biological activities. Further developments on this subject are currently in progress to understand their mechanistic interactions.

Acknowledgment

The authors would like to thank la Commission Universitaire pour le Developpement (CUD, Belgium) for its support.

References

Alabouvette, C., Olivain, C., Migheli, Q., Steinberg, C., 2009. New

Phytologist 184, 529. Al Bay, H., Quaddouri, B., Guaadaoui, A., Touzani, R., Benchat, N.-E., Hamal, A., Taleb, M., Bellaoui, M., El Kadiri, S., 2010. Lett. Drug Des. Disc. 7, 41. Alexander, N.J., Proctor, R.H., McCormick, S.P., 2009. Toxin. Rev. 28, 198.

Armengol, J., Moretti, A., Perrone, G., Vicent, A., Bengoechea, J.A.,

García-Jiménez, J., 2005. Eur. J. Plant Pathol. 112, 123. Bouabdallah, I., Touzani, R., Zidane, I., Ramdani, A., 2007. Catal. Commun. 8, 707.

Bautista-Baños, S., Hernandez-Lauzardo, A.N., Velazquez-Del Valle, M.G., Hernandez-Lopez, M., Ait Barka, E., Bosquez-Molina, E., Wilson, C.L., 2006. Crop Protect. 25, 108. Bouizgarne, B., El Hadrami, I., Ouhdouch, Y., 2006. World J.

Microbiol. Biotechnol. 22, 423. Boussalah, N., Touzani, R., Bouabdallah, I., El Kadiri, S., Ghalem, S.,

2009a. Inter. J. Acad. Res. 1, 137. Boussalah, N., Touzani, R., Bouabdallah, I., El Kadiri, S., Ghalem, S.,

2009b. J. Mol. Catal. A: Chem. 306, 113. Bowers, K., Stevens, T.H., 2005. BBA - Mol. Cell Res. 1744, 438. Carrod, L.P., Grady, F.D. 1972. Antibiotic and Chemotherapy, third

ed., Churchill Livingstone, Edin-burgh, pp. 477. Chauviere-Ramazeilles, C., Mecanismes d'action leishmanicide des esters d'acides amines et de peptides dans le modele d'infection cutanee murine par leishmania amazonensis = Leishmanicidal activity of amino acid and dipeptide esters on the murine cutaneous leishmaniasis by Leishmania amazonensis. These d'Universite de Paris 06, Paris, France. 1990. Cebollero, E., Reggiori, F., 2009. BBA - Mol. Cell Res. 1793, 1413. Cummings, J.A., Miles, C.A., Du Toit, L.J., 2009. Plant Dis. 93, 1281. Daboussi, M.-J., Capy, P., 2003. Annu. Rev. Microbiol. 57, 275. De Waele, D., Elsen, A., 2007. Annu. Rev. Phytopathol. 45, 457. Dvoretzky, I., Richter, G.H., 1950. J. Org. Chem. 15, 1285. El Kodadi, M., Benamar, M., Bouabdallah, I., Zyad, A., Malek, F., Touzani, R., Ramdani, A., Melhaoui, A., 2007. Nat. Prod. Res. 21, 947.

El Kodadi, M., Malek, F., Touzani, R., Ramdani, A., 2008. Catal. Commun. 9, 966.

El Modafar, C., El Boustani, E., Rahioui, B., El Meziane, A., El

Alaoui-Talibi, Z., 2006. Biol. Plant. 50, 697. Fierro, F., Martin, J.F., 1999. Crit. Rev. Microbiol. 25, 1. Fravel, D., Olivain, C., Alabouvette, C., 2003. New Phytologist 157, 493.

Garbacia, S., Hillairet, C., Touzani, R., Lavastre, O., 2005. Collect.

Czech. Chem. Commun. 70, 34. Gordon, T.R., Martyn, R.D., 1997. Annu. Rev. Phytopathol. 35, 111. Govindappa, M., Lokesh, S., Ravishankar Rai, V., Rudra Naik, V.,

Raju, S.G., 2010. Arch. Phytopathol. Plan. Protect. 43, 26. Haas, D., Defago, G., 2005. Nat. Rev. Microbiol. 3, 307. Jaiti, F., Kassami, M., Meddich, A., El Hadrami, I., 2008. J.

Phytopathol. 156, 641. Johnson, D.S., Li, J.J., in: The Art of Drug Synthesis, Wiley-

Intersience, 2007, A John Wiley & Sons, Inc. Publications. Lodewyckx, C., Vangronsveld, J., Porteous, F., Moore, E.R.B., Taghavi, S., Mezgeay, M., Van der Lelie, D., 2002. Crit. Rev. Plant Sci. 21, 583. Lori, G.A., Wolcan, S.M., Larran, S., 2008. J. Plant Pathol. 90, 173. Manriquez, V., Galdamez, A., Veliz, B., Rovirosa, J., Diaz-Marrero, A.R., Cueto, M., Darias, J., Martinez, C., San-Martin, A., 2009. J. Chil. Chem. Soc. 54, 314. McDonald, B.A., Linde, C., 2002. Annu. Rev. Phyto. 40, 349. Pantelides, I.S., Tjamos, S.E., Striglis, I.A., Chatzipavlidis, I., Paplo-

matas, E.J., 2009. Biol. Control 50, 30. Paparu, P., Dubois, T., Gold, C.S., Niere, B., Adipala, E., Coyne, D.,

2008. Microb. Ecol. 55, 561. Pedras, M.S.C., Ahiahonu, P.W.K., 2005. Phytochemical 66, 391. Rawsthorne, H., Phister, T.G., 2009. Lett. Appl. Microbiol. 49, 652. Robinson, P H., Erasmus, L.J., 2009. Anim. Feed Sci. Tech. 149, 185. Roh, S.-G., Park, Y.-C., Park, D.-K., Kim, T.-J., Jeong, J.H., 2001.

Polyhedron 20, 1961. Scarpellini, M., Wu, A.J., Kampk, J.W., Pecoraro, V.L., 2005. Inorg. Chem. 44, 5001.

Schenk, P.M., Choo, J.H., Wong, C.L., 2009. CAB Rev. Perspec.

Agric., Veter. Sci., Nutri. Natur. Reso. 4, 124. Sharma, R., Chisti, Y., Banerjee, U.C., 2001. Biotechnol. Adv. 19, 627. Spadoni, G., Balsamini, C., Bedini, A., Duranti, E., Tontini, A., 1992.

J. Heterocycl. Chem. 29, 305. Stukenbrock, E.H., McDonald, B.A., 2008. Annu. Rev. Phytopathol. 46, 75.

Tamaki, H., 2007. J. Biosci. Bioeng. 104, 245.

Tan, J., Bednarek, P., Liu, J., Schneider, B., Svatos, A., Hahlbrock,

K., 2004. Phytochemical 65, 691. Thangavelu, R., Palaniswami, A., Velazhahan, R., 2004. Agric.

Ecosyst. Environ. 103, 259. Touzani, R., Garbacia, S., Lavastre, O., Yadav, V.K., Carboni, B.,

2003. J. Comb. Chem. 5, 375. Touzani, R., Ramdani, A., Ben-Hadda, T., El Kadiri, S., Maury, O.,

Le Bozec, H., Dixneuf, P.H., 2001. Synth. Commun. 31, 1315. Touzani, R., Vasapollo, G., Scorrano, S., Del Sole, R., Manera, M.G.,

Rella, R., El Kadiri, S., 2011. Mater. Chem. Phys. 126, 375. Van Der Does, H.C., Rep, M., 2007. Mol. Plant-Microbe Interact. 20, 1175.

Waring, M.J., Ben-Hadda, T., Kotchevar, A.T., Ramdani, A., Touzani, R., El Kadiri, S., Hakkou, A., Bouakka, M., Ellis, T., 2002. Molecules 7, 641. Weller, D.M., Raaijmakers, J.M., McSpadden Gardener, B.B.,

Thomashow, L.S., 2002. Annu. Rev. Phytopathol. 40, 309. Weyens, N., van der Lelie, D., Taghavi, S., Vangronsveld, J., 2009.

Curr. Opin. Biotechnol. 20, 248. Yahyi, A., Ettouhami, A., Radi, S., Zidane, I., Hakkou, A., Bouakka,

M., 2007. Lett. Drug Des. Disc. 4, 382. Zumbuehl, A., Stano, P., Sohrmann, M., Dietiker, R., Peter, M., Carreira, E.M., 2009. ChemBioChem 10, 1617.