86,692 research outputs found
SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL A1 ADENOSINE RECEPTOR AGONISTS
No full textA1 adenosine receptor (A1AR) is the best characterized subtype of the four known adenosine receptors.1 Selective A1AR agonists show neuro- and cardio-protective effects, reduce intraocular pressure in glaucoma, and have anticonvulsivant activity. The majority of A1AR agonists are adenosine derivatives and even though many efforts have been carried out, only few drugs in advanced clinical studies are A1AR agonists. The main
problem is represented by the significant cardiovascular side effects (bradicardia and hypotension).1 In our previous studies we found that the replacement of the 5’-hydroxy-group by a chlorine atom in N6-substituted adenosine derivatives, improved both the A1AR affinity and selectivity. 5’-Chloro-5’-deoxy-N6-(±)-endo-
norbornyl-adenosine (5’Cl5’d-(±)-ENBA) resulted a potent and highly selective A1AR2 agonist showing
analgesic effects in a mice model of neuropathic pain.3 Interestingly, at analgesic doses it did not lower blood pressure and locomotor activity in mice.3 Moreover, it reduced dyskinesia evoked by L-DOPA in a mice model of Parkinson disease.4
Based on these interesting findings, a novel series of 5’-modified N6-substitued adenosine derivatives was synthesized and tested in human A1, A2A, A2B, and A3 adenosine receptors binding assay. The most potent and

selective compounds of the series were also assayed in a formalin test in mice. The results of this work will be discussed.
1Fredholm, B.B.; IJzerman, A.P.; Jacobson, K.A.; Linden, J.; Muller, C.E. Pharmacol. Rev. 2011, 63, 1-34.
2Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.;
Grifantini, M. J. Med. Chem. 2009, 52, 2393−2406.
3(a) Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712−13726. (b) Luongo, L.; Guida, F.; Imperatore, R.; Napolitano, F.; Gatta, L.; Cristino, L.; Giordano, C.; Siniscalco, D.; Di Marzo, V.; Bellini, G.; Petrelli, R.; Cappellacci, L.; Usiello, A.; de Novellis, V.; Rossi, F.; Maione, S. Glia 2014, 62, 122−132.
4Mango, D.; Bonito-Oliva, A.; Ledonne, A.; Cappellacci, L.; Petrelli, R.; Nisticò, R.; Berretta, N.; Fisone, G.; Mercuri, N.B. Exp. Neurol. 2014, 261, 733−743
Novel N6/5’-Disubstituted Adenosine Derivatives As A1 Adenosine Receptor Agonists: Synthesis, Binding Assay And Antinociceptive Activity
No full textAdenosine is a regulatory nucleoside that can be generated in response to cellular stress and tissue damage as well as during episodes of tissue hypoxia or inflammation. It acts on specific G-protein coupled receptors that have been classified into four subtypes (A1, A2A, A2B and A3) on the basis of their structures and signal transduction systems.
Selective A1 adenosine receptor (A1AR) agonists have antinociceptive, antiarrhythmic and neuro- and cardioprotective effects. There is a large body of evidence to suggest that A1AR agonists produce antinociception at spinal cord level as well as at supraspinal level. Our previous work showed that replacement of the 5′ -hydroxy-group by a chlorine atom in N6-substituted adenosine derivatives increased selectivity for A1AR [1]. 5′-Chloro-5′-deoxy-N6-(±)-(endo-norborn-2-yl)-adenosine (5′Cl5′d-(±)- ENBA) displayed high A1AR affinity and selectivity. It was shown to reduce both mechanical allodynia and thermal hyperalgesia in a mice model of neuropathic pain without affecting motor and cardiovascular functions [2]. Moreover, it reduced dyskinesia evoked by L-DOPA in a mice model of Parkinson’s disease [3].
In this work, novel N6/5’-disubstituted adenosine derivatives were synthesized and evaluated for analgesic activity in a formalin test in mice. The most potent compound of the series was found to inhibit the second phase of the nocifensive response induced by intrapaw injection of formalin at a dose of 2 mg/kg i.p. [2] Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393−2406.
[3] (a) Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712−13726. (b) Luongo, L.; Guida, F.; Imperatore, R.; Napolitano, F.; Gatta, L.; Cristino, L.; Giordano, C.; Siniscalco, D.; Di Marzo, V.; Bellini, G.; Petrelli, R.; Cappellacci, L.; Usiello, A.; de Novellis, V.; Rossi, F.; Maione, S. Glia 2014, 62, 122−132.
[4] Mango, D.; Bonito-Oliva, A.; Ledonne, A.; Cappellacci, L.; Petrelli, R.; Nisticò, R.; Berretta, N.; Fisone, G.; Mercuri, N.B. Exp. Neurol. 2014, 261, 733−743
Effects of 5'-chloro-5'-deoxy-N6-(±)-endo-norbornyl-adenosine, a potent and highly selective A1 adenosine receptor agonist, on neuropathic pain-induced behavioural and morphological changes in spinal microglia
No full textThis study was undertaken in order to investigate the effect of chronic treatment with 5'-chloro-5'-deoxy-N6-(±)-endo-norbornyladenosine (5'Cl5'd-(±)-ENBA),1 a potent and highly selective adenosine A1 receptor agonist, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the spared nerve injury (SNI). Chronic systemic administrations of 5'Cl5'd-(±)-ENBA (0.5 mg/kg, i.p once a day) reduced both thermal hyperalgesia and mechanical allodynia 3 and 7 days after SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A1 receptor antagonist. SNI induced spinal changes on microglial activation ipsilaterally to the nerve injury. Moreover, 5'Cl5'd-(±)-ENBA significantly reduced microglial activation in vitro. In particular pre-incubation with 5'Cl5'd-(±)-ENBA prevented the microglial morphological changes induced by LPS, ATP, LPS+ATP challenges. Our results demonstrated an involvement of A1 receptors in the increase of nociceptive thresholds and in spinal changes occurred in neuropathic pain. In addition, 5'Cl5'd-(±)-ENBA antiallodynic and antihyperalgesic effects could be mediated by the A1 receptors expressed on microglial cells.
(1) Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393-2406
SYNTHESIS AND PHARMACOLOGICAL CHARACTERIZATION OF RIBOSE-MODIFIED ADENOSINE DERIVATIVES AS P1 RECEPTOR LIGANDS
No full textAdenosine, the natural ligand of P1 receptors, is implicated in the control of many physiological and pathological conditions such as inflammation, pain, cardiovascular and central nervous system (CNS) diseases.1
P1 receptors belong to the large family of GPCR receptors and are divided in four subtypes: A1, A2A, A2B and A3 adenosine receptors (ARs). Even though a large number of P1 ligands have been synthesized and characterized byin vitro and in vivo pharmacological studies, only very few of them are commercially available.
Modifications at the ribose moiety and substitution at the N6-position of adenosine, lead to adenosine derivatives endowed with increased potency at A1 or A3AR. Our previous SAR studies showed that the replacement of OH at 5’-position of the ribose moiety of N6-substituted adenosine derivatives by a chlorine improved A1AR potency and selectivity versus A3AR, with 5′-chloro-5′-deoxy-N6-(±)-(endo- norborn-2-yl)-adenosine (5′Cl5′d-(±)-ENBA) as one of the most potent and selective A1AR agonists,2 while a 5’-C-ethyl-tetrazolyl moiety maintained the A1AR potency, but restored high A3AR affinity, leading to very potent dual A1AR and A3AR ligands.3 Interestingly, both modifications at 5’-position of adenosine derivatives brought to human A3AR antagonism.
In order to further explore the structural determinants of this class of P1 ligands, a new series of ribose- modified N6-substituted adenosine derivatives was synthesized and their pharmacological profile was assayed. The results of this study will be discussed.References
1. Jacobson KA, Muller CE, Neuropharmacology 2015, doi: 10.1016/J.neuropharm.2015.12.001.
2. (a) Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393−2406. (b) Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712−13726. (c) Luongo, L.; Guida, F.; Imperatore, R.; Napolitano, F.; Gatta, L.; Cristino, L.; Giordano, C.; Siniscalco, D.; Di Marzo, V.; Bellini, G.; Petrelli, R.; Cappellacci, L.; Usiello, A.; de Novellis, V.; Rossi, F.; Maione, S. Glia 2014, 62, 122−132.
3. Petrelli, R.; Torquati, I.; Kachler, S.; Luongo, L.; Maione, S.; Franchetti, P.; Grifantini, M.; Novellino, E.; Lavecchia, A.; Klotz, K.-N-; Cappellacci, L. J. Med. Chem. 2015, 58, 2560-2566
N6-substituted-5'-C-ethyi-tetrazolyl-adenosine derivatives: potent dual acting A1 and A3 adenosine receptor iigands with analgesic properties
No full textAdenosine (Ado) is the endogenous ligand of a family of G-protein coupied receptors (GPCRs) represented by four subtypes: Ai, A2A, A2B, and A3 adenosine receptors (ARs). They are widely distributed in all the human body including the central nervous system (CNS), peripheral neurons, cardiovascular system, respiratory tract and immune system [1].
Affinity and selectivity towards the four ARs can be modulated through substitutions at both purine and sugar moiety of adenosine. The replacement of the 5'-hydroxyl group with a chlorine atom in /V6-substituted adenosine derivatives led to discovery of 5'-chloro-5'-deoxy-/V6-(±)-(endo-norborn-2-yl)- adenosine (5'CI5'd-(±)-ENBA), a potent and selective A1AR agonist that showed analgesic effects in mice without affecting cardiovascular and motor functìons [2].
Introduction of a 5'-C-ethyltetrazol-2-yl group, together with the appropriate N6-substitution in adenosine derivatives, furnished compounds endowed with an increased affinity versus both hA1AR and hA3AR, reaching affinities in subnanomolar range [3].
In this work, a new series of 5'-C-ethyltetrazol-2-yl-N6-substituted adenosine derivatives were designed, synthesized and tested in vitro in binding and functional assays and in vivo in a mouse model of pain. The molecular features necessary for the hA1- and hA3AR recognition and activation by this series of derivatives were explained through an in silice receptor-driven approach. [1] K. A. Jacobson and C. E. Muller, Neuropharmacology 104(2016) 31-49.
[2] L. Luongo, R. Petrelli, L. Gatta, C. Giordano, F. Guida, P. Vita, P. Franchetti, M. Grifantini, V. De Novellls, L. Cappellacci, and S. Maione, Molecules 17 (2012) 13712-13726.
[3] R. Petrelli, I. Torquati, S. Kachler, L. Luongo, S. Maione, P. Franchetti, M. Grifantini, E. Novellino, A. Lavecchia, K.-N. Klotz, and L. Cappellacci, J. Med. Chem. 58 (2015) 2560-2566
Highly potent dual acting A1 and A3 adenosine receptor ligands: synthesis, binding, functional assays and analgesic effects in mice
No full textAdenosine (Ado) is a purine nucleoside endowed with many different physiological and pathological functions. Many studies support the fact that Ado acts as a neurotrasmitter and neuromodulator, and as an endogenous agonist on adenosine receptors (ARs). ARs belong to the superfamily of G-protein- coupled receptors (GPCRs) and are represented by four subtypes: A1, A2A, A2B, and A3 ARs (1). They are found in almost all kind of tissue: central nervous system (CNS), peripheral neurons, cardiovascular system, respiratory tract and immune system (2). Due to the wide distribution of ARs throughout the body, there is a substantial possibility that Ado ligands will have unwanted effects in non target tissues.
One way to overcome adverse effects is the use of multitarget drugs (3). A multitarget drug may display an improved therapeutic efficacy compared to a highly selective one. In fact, multitarget activities may potentiate the effect of treatment either additively or synergistically. Moreover, a multitarget drug has the advantage of following only one pharmacokinetic and metabolic pattern, thus overcoming the limits of combination therapy.
Substitutions at both purine and sugar moiety of adenosine results on AR ligands endowed with different affinity and selectivity at the four AR subtypes (4). Potent and highly selective A1AR agonists have been previously obtained by replacement of the 5’-hydroxyl group with a chlorine atom in N6-substituted-adenosine derivatives (5). 5’-Chloro-5’-deoxy-N6-(±)-(endo-norborn-2-yl)- adenosine (5’Cl5’d-(±)-ENBA) showed analgesic effects in mice without affecting cardiovascular and motor functions (6).
Combining a 5’-C-ethyltetrazol-2-yl group with the appropriate N6-substitution in adenosine derivatives led to an increased affinity versus both hA1AR and hA3AR, reaching subnanomolar values, while remaining agonists at hA1 and antagonists at hA3AR (7).
In this work a new series of 5’-C-ethyltetrazol-2-yl-N6-substituted adenosine derivatives were synthesized and studied both in vitro in binding and functional assays and in vivo in a mouse model of pain. Through an in silico receptor-driven approach, the molecular bases of the hA1- and hA3AR recognition and activation of this series of 5’-C-ethyl-tetrazolyl derivatives were explained.
References: 1. Fredholm, B. B.; IJzerman, A. P.; Jacobson, K. A.; Linden, J.; Muller, C. Pharmacol. Rev. 2011, 63, 1-34. 2. Jacobson, K. A.; Muller, C. E. Neuropharmacology 2016, 104, 31-49. 3. Anighoro, A.; Bajorath, J.; Rastelli, G. J. Med. Chem. 2014, 57, 7874-7887. 4. Petrelli, R.; Grifantini, M.; Cappellacci, L. Curr. Med. Chem. 2016, 23, 3118-3135. 5. Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393-2406. 6. Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712-13726. 7. Petrelli, R.; Torquati, I.; Kachler, S.; Luongo, L.; Maione, S.; Franchetti, P.; Grifantini, M.; Novellino, E.; Lavecchia, A.; Klotz, K.- N.; Cappellacci, L. J. Med. Chem. 2015, 58, 2560-2566
2'-C-Methyl-2-chloro-N6-cyclopentyladenosine, a potent and highly selective A1 adenosine receptor agonist, has antinociceptive activity and modulates RVM on-and-off cell activities
No full textThe study was undetaken to investigate the effect of 2'-C-methyl-2-chloro-N6-cyclopentyladenosine (2'-Me-CCPA), a potent and highly selective A1 adenosine receptor agonist [1], on antinociceptive responses and on spontaneous activity of ON- and OFF-neurons of rostral ventromedial medulla (RVM). Moreover, we investigate whether the intra-periaqueductal grey (PAG) microinjection of 2'-Me-CCPA induced changes in the tail flick latencies, as well as tail-related changes in RVM cell activities. Systemic administrations of 2'-Me-CCPA (2-5 mg/Kg, i.p.), 10 min before formalin, reduced tha late hyperalgesic phase; in formalin test, these effecs were prevented by DPCPX (3 mg/Kg, i.p.), a A1 receptor antagonist, but not by DPMX (3 mg/Kg, i.p.), a A2 receptor antagonist. Intra-PAG microinjections of 2'-Me-CCPA (0.5-1 nmol/rat) increased the tail flick latencies, delayed the tail flick-related onset to ON-cell burst and decreased the duration of OFF-cell ongoing activities, in a dose-dependent manner. These electrophysiological effects were prevented by DPCPX (1 nmol/rat). In cocnlusion, this study confirms the role of A1 receptors in the modulation of inflammatory pain and suggests a critical role of PAG purinergic system for the control of acute and chronic pain. [1] Cappellacci L et al J Med Chem 48, 1550-1562, 200
Design, synthesis and biological evaluation of N6/5’-disubstituted adenosine derivatives as A1 adenosine receptor agonists
No full textAdenosine is an endogenous purine nucleoside that modulates a variety of physiological functions as a result of its activation of specific G protein-coupled receptors defined as A1, A2A, A2B, and A3 adenosine receptors (ARs) (1).
The A1 adenosine receptor (A1AR) is the best characterized adenosine receptor subtype. Selective A1AR agonists mediate neuro- and cardioprotective effects, reduce lipolysis in adipose tissue, and intraocular pressure in glaucoma (1,2). The A1AR is abundantly expressed in spinal cord and other neuronal tissue, and its activation produced pain-relieving effects in a number of preclinical animal models (3). Our previous works discovered that combining the appropriate 5- and N6-substitution in adenosine derivatives, highly selective human (h) A1AR agonists (4) or highly potent dual hA1AR agonists and hA3AR antagonists can be obtained (5). The substitution of OH at the 5-position of N6- substituted adenosine derivatives with a chlorine atom is not only well tolerated by the hA1AR but even improves the A1AR selectivity and affinity. 5-Chloro-5-deoxy-N6-(±)-endo-norbornyl- adenosine (5Cl5d-(±)-ENBA) turned out to be a potent and the most selective human and mouse (m) A1AR agonist vs A3AR so far known (4,6) with analgesic effects in a mouse model of neuropathic pain (7). Moreover, it was found to reduce the dyskinesia caused by L-DOPA in a mouse model of Parkinson disease (PD) (8) and the tremor in a harmaline-induced model of essential tremor (ET), suggesting that A1AR may be a potential target also for the treatment of ET (9).
In order to explore novel combinations of 5-modification and N6-substitution leading to potent and selective A1AR agonists, a series of 5,N6-disubstituted adenosine derivatives was synthesized and evaluated for affinity and selectivity at all cloned hAR subtypes.
References: 1. Jacobson, K. A.; Muller, C. E. Neuropharmacology 2016, 104, 31-49. 2. Donegan, R. K. and Lieberman, R. L. J. Med. Chem. 2016, 59, 788-809. 3. Sawynok, J. Adenosine receptor targets for pain. Neuroscience, 2016, 338, 1- 18. 4. Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393-2406. 5. Petrelli, R.; Torquati, I.; Kachler, S.; Luongo, L.; Maione, S.; Franchetti, P.; Grifantini, M.; Novellino, E.; Luongo, L.; Maione, S.; Franchetti, P.; Grifantini, M.; Novellino, E.; Lavecchia, A.; Klotz, K.- N.; Cappellacci, L. J. Med. Chem. 2015, 58, 2560-2566. 6. Carlin, J. L.; Jain, S.; Gizewski, E.; Wan, T. C.; Tosh, D. K.; Xiao, C.; Auchampach, J. A.; Jacobson, K. A.; Gavrilova, O.; Reitman, M. L. Neuropharmacology 2017, 114, 101-113. 7. Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712-13726. 8. Mango, D.; Bonito-Oliva, A.; Ledonne, A.; Cappellacci, L.; Petrelli, R.; Nisticò, R.; Berretta, N.; Fisone, G.; Mercuri, N.B. Exp. Neurol. 2014, 261, 733-743. 9. Kosmowska, B.; Ossowska, K.; Glowacka, U.; Wardas, J. CNS Neurosci. Ther. 2017, DOI: 10.1111/cns.1269
5’-CHLORO-5’-DEOXY-N6-SUBSTITUTED ADENOSINE DERIVATIVES: SYNTHESIS, ADENOSINE RECEPTOR AFFINITY AND ANTINOCICEPTIVE ACTIVITY
No full textNeuropathic pain, defined as “pain caused by a lesion or dysfunction of the nervous system”, is a personally devastating and costly condition affecting 3-8% of the population in developed countries. It may results from a wide variety of causes (including degenerative spinal disease, diabetes cancer and various infection diseases), that affect the brain, spinal cord and/or peripheral nerves. Existing treatments have limited effectiveness, being effective in some, but not all, neuropathic pain syndromes and producing relatively frequent adverse effects. Today’s first-line treatment of neuropathic pain relies predominantly on anticonvulsivant and antidepressant drugs, future pharmacological therapy may depend on agents that act on different targets.
Adenosine is the endogenous agonist of four members of G-protein-coupled receptors (A1, A2A, A2B and A3 adenosine receptors, ARs) and has a wide range of biological effects. There is growing evidence that AR agonists are attractive therapeutic agents for a number of conditions including pain, cardiac arrhythmias, myocardial perfusion imaging, cardiac ischemia, inflammation and certain types of cancer. The A1 adenosine receptor (A1AR) is abundantly expressed in spinal cord and other neuronal tissues. There is evidence that A1AR agonists produce antinociception at the spinal cord as well as at supraspinal level (1).
We have previously reported that 5’-chloro-5’-deoxy-N6-(±)-(endo-norborn-2-yl)-adenosine (5’Cl5'd-(±)-ENBA) has emerged as a potent and highly selective full agonist of human A1AR (hA1AR (Ki) = 0.51 nM, hA2AAR = 1,340 nM, hA2BAR = 2,740 nM, hA3AR = 1,290 nM) (2). Moreover, 5’Cl5’d-(±)-ENBA showed acute nocifensive effect in the formalin test and anti-neuropathic properties in a model of neuropathic pain, the spared nerve injury (SNI) of the sciatic nerve in mice (3). Interestingly, 5’Cl5’d-(±)-ENBA did not modify motor coordination and blood pressure or heart rate in unanaesthetized sham and SNI mice. The interesting biological properties of 5’Cl5’d-(±)-ENBA demonstrated that the substitution of 5’-hydroxyl group in adenosine analogues with a chlorine is well tolerated by A1AR, and seems reduce the cardiovascular side effects of A1AR full agonists.
As a proof of the concept, 5’-chloro-5’-deoxy-N6-substituted adenosine/2-chloro-adenosine derivatives were synthesized and evaluated for affinity and selectivity at all human adenosine receptor subtypes. Moreover, antinociceptive activity in a formalin test in mice was assayed. The results of these studies will be discussed.
(1) Sowa, N.A.; Voss, M.K.; Zylka, M.J. Mol. Pain 2010, 6, 2–8.
(2) Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393-2406.
(3) Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; de Novellis, V.; Cappellacci, L.; Maione, S . Molecules 2012, 17, 13712-13726
Origanum syriacum subsp. syriacum: from an ingredient of Lebanese 'manoushe' to a source of effective and eco-friendly botanical insecticides
No full textOriganum syriacum subsp. syriacum, also known as ‘Za’tar’ is an aromatic shrub native to Lebanon and cultivated in other Middle East countries. The plant leaves enjoy a high reputation as a traditional remedy against cardiovascular, respiratory and infectious diseases. In addition, they are a famous component of the Lebanese pizza (“manoushe”). Starting from its safety for humans, here O. syriacum subsp. syriacum was selected to assess the insecticidal efficacy of its leaf essential oil (EO) and its major constituent carvacrol against two key agricultural pests, namely the noctuid Spodoptera littoralis and the aphid Myzus persicae, as well as on the fly pest Musca domestica. Furthermore, the Za’tar EO potential impact on beneficial organisms such as the aphid predator Harmonia axyridis and the earthworm Eisenia fetida, which is used in the vermicomposting process, was assessed. GC–MS analysis highlighted the phenolic monoterpene carvacrol as the predominant component (83%) of Za’tar EO. Toxicity of O. syriacum subsp. syriacum EO was noteworthy, showing LC50/LD50 of 103.3 μg larva−1, 2.1 mg L−1 and 58.7 μg adult−1 on S. littoralis, M. persicae and M. domestica, respectively, which were partly consistent with those of its major component carvacrol (38.3 μg larva-1, 1.6 mL L−1 and 59.3 μg adult-1, respectively). When tested up to 3.8 mL L−1 and 200 mg kg−1 on H. axyridis and E. fetida, this EO was not toxic, at variance with α-cypermethrin, which caused 100% mortality at 1 mL L−1 and 25 mg kg−1, respectively. Taken together, these results promote carvacrol-rich Za’tar EO as a promising reservoir of green insecticides to be used for managing insect pests and vectors of economic relevance
- …
