Three novel synthetic amides of adipic acid protect Capsicum anuum plants against the necrotrophic pathogen Alternaria solani Vı ´ctor Flors a , Carmen Miralles a , Carmen Gonza ´lez-Bosch b , Miguel Carda c , Pilar Garcı ´a-Agustı ´n a, * a Fisiologı ´a Vegetal, Departamento de Ciencias Experimentales, Campus Riu Sec, ESTCE, Universitat Jaume I, 12071 Castello ´n, Spain b Departamento de Bioquı ´mica, Universitat de Vale `ncia, IATA (CSIC) Polı ´gono de la Coma s/n Paterna, 46980 Valencia, Spain c Quı ´mica Orga ´nica, Departamento de Quı ´mica Inorga ´nica y Orga ´nica, Campus Riu Sec, ESTCE, Universitat Jaume I, 12071 Castello ´n, Spain Accepted 31 October 2003 Abstract Three novel amides of adipic acid, 5-carbamoil ethyl pentanoate (N 1 ), 5-(2-furfurylmethylcarbamoil) ethyl pentanoate (N 2 ) and 5-(3- aminopropylcarbamoil) ethyl pentanoate (N 3 ) were synthesized and their resistance-inducing activity was studied on pepper (Capsicum annuum) plants. Treatment with low doses of each amide protected pepper plants against the pathogen Alternaria solani,N 1 being the most effective. Although their mode of action is still unknown, prechallenge studies demonstrated the induction of the phenylpropanoid pathway and an antisenescence effect. These effects were previously shown for other mixtures and derivatives of adipic acid. These new chemicals showed no antimicrobial activity at doses much higher than those used for plant treatments. This fact supports the idea that they are acting mainly via planta by inducing natural resistance pathways. Treatments based on these novel chemicals produce no phytotoxic effects and improve plant growth and development. For that reason, they could constitute an attractive alternative to fungicides. It is interesting to note that they are adipic acid derivatives, a compound used as alimentary additive with non toxic properties. Obviously a complete safety study is necessary before these chemicals could be commerzialized. q 2003 Elsevier Ltd. All rights reserved. Keywords: Carboxylic acid; Furfurylamine; 1,3-Diaminepropane; Adipic acid monoethyl ester; Sugar analogs; Pepper; Plant–fungus interaction 1. Introduction Plants defend themselves against pathogen attack by means of constitutive and inducible protective systems [11]. Several biological and synthetic compounds are capable of controlling a large variety of plant diseases by inducing natural resistance in treated plants. For that reason, these compounds are known as inducers. Some of the chemical inducers best characterized are 2,6-dichloro isonicotinic acid (INA) [17], benzo-(1,2,3)-thiadiazole-7-carbotionic acid S-methyl ester (BTH) [16], BABA (b-aminobutyric acid) [25] and chitosan [1]. The mode of action of these compounds is not yet clear but they probably act at different points on the specific signal transduction pathways that mediate the defense responses. With the exception of chitosan, direct antibiotic activity has been discarded for most of them [14,25]. Chitosan seems to play a dual function, activating protective processes in the plants and acting directly on fungal growth in a concentration- dependent manner [6]. Nowadays, the development of novel resistance-inducing chemicals represents an attractive alterna- tive to protect crops against pathogens. We have recently reported the effects of a chemical mixture of adipic acid monoethyl ester, furfurylamine and a glucose derivative (FGA) on senescence and plant–fungus interaction in Solanaceae plants [7]. Exogenous application of this mixture to tomato and pepper plants induced protection against Phytophthora sp. infection. Prechallenge studies demon- strated that the inducing activity of FGA is in part mediated by the activation of the phenylpropanoid pathway and by an antisenescence effect. Otherwise, a novel synthetic compound derived from components of the mixture FGA and called 0885-5765/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.pmpp.2003.10.007 Physiological and Molecular Plant Pathology 63 (2003) 151–158 www.elsevier.com/locate/pmpp * Corresponding author. Tel.: þ 34-964-729-407; fax: þ34-964-728-066. E-mail address: garciap@exp.uji.es (P. Garcı ´a-Agustı ´n). Abbreviations: bME, b-mercaptoethanol; CHI, chalcone isomerase; DTT, ditiothreitol; DAP, 1,3-diaminepropane; PAL, phenylalanine ammonia-liase; RT, room temperature; SA, salicylic acid; SAR, systemic acquired resistance; TMV, tobacco mosaic virus; TOGE, 1,2,3,4-tetra-O- acetyl-6-ethyladipate-D-glucose.