Insecticidal activity of indole derivatives against Plutella xylostella and selectivity to four non-target organisms.

The diamondback moth Plutella xylostella (Linnaeus, 1758) (Lepidoptera: Plutellidae) is a destructive pest of brassica crops of economic importance that have resistance to a range of insecticides. Indole derivates can exert diverse biological activities, and different effects may be obtained from small differences in their molecular structures. Indole is the parent substance of a large number of synthetic and natural compounds, such as plant and animal hormones. In the present study, we evaluate the insecticidal activity of 20 new synthesized indole derivatives against P. xylostella, and the selectivity of these derivatives against non-target hymenopteran beneficial arthropods: the pollinator Apis mellifera (Linnaeus, 1758) (Hymenoptera: Apidae), and the predators Polybia scutellaris (White, 1841), Polybia sericea (Olivier, 1791) and Polybia rejecta (Fabricius, 1798) (Hymenoptera: Vespidae). Bioassays were performed in the laboratory to determine the lethal and sublethal effects of the compounds on P. xylostella and to examine their selectivity to non-target organisms by topical application and foliar contact. The treatments consisted of two synthesized derivatives (most and least toxic), the positive control (deltamethrin) and the negative control (solvent). The synthesized compound 4e [1-(1H-indol-3-yl)hexan-1-one] showed high toxicity (via topical application and ingestion) and decreased the leaf consumption by P. xylostella, displaying a higher efficiency than the pyrethroid deltamethrin, widely used to control this pest. In addition, the synthesized indole derivatives were selective to the pollinator A. mellifera and the predators P. scutellaris, P. sericea and P. rejecta, none of which were affected by deltamethrin. Our results highlight the promising potential of the synthesized indole derivatives for the generation of new chemical compounds for P. xylostella management.

Evaluation of (-)-borneol derivatives against the Zika vector, Aedes aegypti and a non-target species, Artemia sp.

Zika, dengue, and chikungunya are vector-borne diseases of pronounced concern transmitted by the mosquito Aedes aegypti Linn. (Diptera: Culicidae). The most important method to avoid outbreaks is to control mosquito spreading by the employment of insecticides and larvicides. Failure to control mosquito dispersal is mostly accounted to Ae. aegypti resistance to currently available larvicides and insecticides, encouraging the development of novel pesticides. In addition, the excessive use of larvicides poses serious threats to human health and the environment. Evaluation of natural products as larvicides in an attempt to overcome this situation is often found in the literature because products originated from nature are considered less toxic to non-target species and more eco-friendly. (-)-Borneol is a bicyclic monoterpene present in essential oils with moderate larvicidal activity. On account of these facts, it was of our interest to synthesize (-)-borneol ester derivatives aiming to study its structure-activity relationships against Ae. aegypti larvae. With the goal to estimate toxicity to a non-target species, evaluation of the lethal concentration 50% (LC50) on Artemia sp. (Artemiidae) and calculation of selectivity towards Ae. aegypti were carried out. The most potent derivative, (-)-Bornyl chloroacetate, exhibited the highest suitability index, demonstrating lower environmental toxicity than other borneol ester derivatives. A parabolic relationship between (-)-borneol esters larvicidal activity and partition coefficient (Log P) was achieved and a correlation equation obtained, validating the importance of lipophilicity to the larvicidal activity of these compounds.

Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil Constituents.

Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, all evaluated compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and 568.1 µg mL-1. Compounds with the best leishmanicidal activity presented a phenolic moiety (IC50 between 25.4 and 82.9 µg mL-1). Alicyclic alcohols ((-)-menthol and isoborneol) and ketones ((-)-carvone) promoted similar activity against the parasite (IC50 between 190.2 and 198.9 µg mL-1). Most of the compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure-activity relationship of these compounds showed the importance of the phenolic structure for the biological action against the promastigote forms of the parasite.

Synthesis, activity, and QSAR studies of tryptamine derivatives on third-instar larvae of Aedes aegypti Linn.

Special attention has been given to the mosquito Aedes aegypti Linn. (Diptera: Culicidae) owing to numerous dengue epidemic outbreaks worldwide. Failure to control vector spreading is accounted for unorganized urban growth and resistance to larvicides and insecticides. Therefore, researchers are currently searching for new and more efficient larvicides and insecticides to aid dengue control measures. Triptamine is known to affect insect behavior, development, and physiology. Expression of this compound in plants has reduced the growth rate of herbivore insects. In view of these facts, it was of our interest to synthesize triptamine amide derivatives as potential larvicides against Ae. aegypti, establishing a Structure-Activity Relationship. Eleven amide derivatives of triptamine were synthesized, characterized, and evaluated for their larvicidal activity against third-instar Ae. aegypti larvae. N-(2-(1H-indol-3-yl)ethyl)-2,2,2-trichloroacetamide exhibited the highest overall larvicidal potency, while N-(2-(1H-Indol-3-yl)ethyl) acetamide displayed the lowest larvicidal potency. A regression equation correlating the larvicidal activity with Log P was obtained. We have found a clear relationship between the larvicidal activity of non-chlorinated compounds and Log P. Analysis of the relationship between Log P and larvicidal activity against Ae. aegypti may be useful in the evaluation of potential larvicidal compounds.

Chemometric studies on potential larvicidal compounds against Aedes aegypti.

The mosquito Aedes aegypti (Diptera, Culicidae) is the vector of yellow and dengue fever. In this study, chemometric tools, such as, Principal Component Analysis (PCA), Consensus PCA (CPCA), and Partial Least Squares Regression (PLS), were applied to a set of fifty five active compounds against Ae. aegypti larvae, which includes terpenes, cyclic alcohols, phenolic compounds, and their synthetic derivatives. The calculations were performed using the VolSurf+ program. CPCA analysis suggests that the higher weight blocks of descriptors were SIZE/SHAPE, DRY, and H2O. The PCA was generated with 48 descriptors selected from the previous blocks. The scores plot showed good separation between more and less potent compounds. The first two PCs accounted for over 60% of the data variance. The best model obtained in PLS, after validation leave-one-out, exhibited q(2) = 0.679 and r(2) = 0.714. External prediction model was R(2) = 0.623. The independent variables having a hydrophobic profile were strongly correlated to the biological data. The interaction maps generated with the GRID force field showed that the most active compounds exhibit more interaction with the DRY probe.

Antinociceptive Activity and Redox Profile of the Monoterpenes (+)-Camphene, p-Cymene, and Geranyl Acetate in Experimental Models.

Objective. To evaluate antinocicpetive and redox properties of the monoterpenes (+)-camphene, p-cymene, and geranyl acetate in in vivo and in vitro experimental models. Methods. Evaluation of the in vitro antioxidant activity of (+)-camphene, p-cymene, and geranyl acetate using different free radical-generating systems and evaluation of antinociceptive actions by acetic acid-induced writhing and formalin-induced nociception tests in mice. Results. p-Cymene has the strongest antinociceptive effect, but (+)-camphene and geranyl acetate also present significant activity at high doses (200 mg/kg). (+)-Camphene had the strongest antioxidant effect in vitro at TBARS and TRAP/TAR assays and also had the highest scavenging activities against different free radicals, such as hydroxyl and superoxide radicals. Sodium nitroprussiate-derived NO production was enhanced by (+)-camphene. Geranyl acetate and p-cymene also presented some antioxidant effects, but with a varying profile according the free radical-generating system studied. Conclusion. (+)-Camphene, p-cymene, and geranyl acetate may present pharmacological properties related to inflammation and pain-related processes, being potentially useful for development of new therapeutic strategies, with limited possibilities for p-cymene and geranyl acetate.

Structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUND: Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS: Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC(50) = 62.3 and 77.0 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC(50) = 93.3 and 71.9 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity and structure-activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1-benzoate-2-methoxy-4-(2-propen-1-yl)-phenol resulted in increased potency. CONCLUSION: Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds.

Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice.

We attempted to identify the antinociceptive and anti-inflammatory actions of the monoterpene p-cymene. Firstly, behavioural screening was carried out to verify the influence of p-cymene [25, 50, and 100 mg/kg intraperitoneal (i.p.)] on the central nervous system (CNS) activity. The antinociceptive activity of p-cymene was evaluated by the acetic acid-induced writhing response, formalin, and hot-plate test, respectively. The leukocyte migration induced by injection of carrageenan was used to assess the anti-inflammatory activity. p-Cymene showed depressant activity on CNS after 4 h of treatment and also a possible action on the autonomous nervous system (ANS), mainly at the dose of 100 mg/kg (i.p.). It was found that p-cymene (50 and 100 mg/kg, i.p.) significantly (p < 0.05) reduced the writhing responses induced by acetic acid. p-Cymene also decreased the licking time in the first and second phase, respectively, of the formalin test. The results of the hot-plate test showed that all doses of p-cymene increased significantly the latency time of the response to the thermal stimulus in both licking and jumping parameters. In addition, there was a significantly (p < 0.05) decreased leukocyte migration at all doses of p-cymene. The experimental data demonstrate that p-cymene possesses antinociceptive and anti-inflammatory activities.

Phytochemical screening, antinociceptive and anti-inflammatory activities of Chrysopogon zizanioides essential oil

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

Investigation of mechanisms involved in (-)-borneol-induced vasorelaxant response on rat thoracic aorta.

The monoterpene (-)-borneol is present in essential oils of several medicinal plants. The aim of this study was to evaluate (-)-borneol effects on rat thoracic aorta artery rings. The cumulative addition of (-)-borneol (10(-9) -3 × 10(-4) M) on a phenylephrine-induced pre-contraction (10(-6) M) promoted a vasorelaxant effect in a concentration-dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl-induced pre-contractions (80 mM). (-)-Borneol (10(-5) -3 × 10(-4 ) M) inhibited contractions induced by cumulative addition of CaCl2 (10(-6) -3 × 10(-2) M) in depolarizing medium without Ca(2+) in a concentration-dependent manner. On S-(-) Bay K 8644-induced pre-contractions (10(-7) M), (-)-borneol did not induce significant changes compared with KCl-induced pre-contractions. In a Ca(2+) -free medium, (-)-borneol (10(-5) , 10(-4) or 10(-3) M) interfered in calcium mobilization from phenylephrine (10(-6) M)- or caffeine (20 mM)-sensitive intracellular stores. The involvement of K(+) channels was evaluated by tetraethylammonium (3 mM), 4-aminopyridine (1 mM) and glibenclamide (10(-5) M) pre-treatment, and (-)-borneol-induced vasorelaxation was markedly attenuated. Thus, this vasorelaxant effect can probably be attributed to calcium influx blockade through voltage-operated calcium channels (CaV L), calcium mobilization from intracellular stores and potassium channels activation.

Carvacrol attenuates mechanical hypernociception and inflammatory response.

Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 µg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

p-Cymene reduces orofacial nociceptive response in mice

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2 percent Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

Structure-activity relationships of larvicidal monoterpenes and derivatives against Aedes aegypti Linn.

In the search for larvicidal compounds against Aedes aegypti L. (Diptera: Culicidae), a collection of monoterpenes were selected and evaluated. R- and S-limonene exhibited the highest larvicidal potency (LC(50)=27 and 30 ppm, respectively), followed by γ-terpinene (LC(50)=56 ppm) and RS-carvone (LC(50)=118 ppm). Structural characteristics which may contribute to the understanding of the larvicidal activity of monoterpenes were empirically identified. The presence of heteroatoms in the basic hydrocarbon structure decreases larvicidal potency. Conjugated and exo double bonds appear to increase larvicidal potency. Replacement of double bonds by more reactive epoxides decreases the larvicidal potency. The presence of hydroxyls in the cyclic structure resulted in decreased potency, probably due to increased polarity indicanting that lipophilicity seems to play an important role in increasing the larvicidal potency in this set of compounds.

Characterisation of the anti-inflammatory and antinociceptive activities and the mechanism of the action of Lippia gracilis essential oil.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Lippia gracilis Schauer, known in Brazil as "Alecrim-da-chapada", is popularly used in folk medicine to treat cough, bronchitis, nasal congestion, and headache. MATERIALS AND METHODS: Lippia gracilis essential oil (EO; 10, 30, and 100mg/kg, p.o.) and the reference drugs morphine (5mg/kg, p.o.) and acetylsalicylic acid (ASA; 200mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortion, formalin-induced licking, and hot plate) or inflammation (formalin-induced licking response and subcutaneous air pouch model). To elucidate the antinociceptive mechanism of action, animals were pre-treated with naloxone (opioid receptor antagonist; 1mg/kg, i.p.), atropine (cholinergic antagonist; 1mg/kg, i.p.) or l-nitro arginine methyl ester (L-NAME; 3mg/kg, i.p.) 30 min prior to oral administration of EO. RESULTS: EO significantly inhibited the number of writhings in acetic acid-induced contortions and the time that the animal spent licking the formalin-injected paw (second phase). All doses of EO increased the baseline and the area under the curve in the hot plate model. The administration of naloxone did not reverse the antinociceptive effect of EO in the acetic acid-induced contortion and formalin-induced licking models. L-NAME and atropine significantly reversed the effect of EO in the models of contortion, formalin, and hot plate. EO also inhibited the inflammatory process induced by subcutaneous carrageenan injection, reducing cell migration, exudate volume, extravased protein, and inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IFN-γ) produced in the pouch. CONCLUSIONS: Our results indicate that the essential oil from Lippia gracilis produces an antinociceptive effect that could be potentially mediated by cholinergic receptors and the nitric oxide pathway. Our data also suggest that the anti-inflammatory activity caused by EO exposure occurs through inhibition of nitric oxide and PGE2 production.

Characterisation of the anti-inflammatory and antinociceptive activities of the Hyptis pectinata (L.) Poit essential oil.

AIM OF THE STUDY: Hyptis pectinata Poit (Lamiaceae) is grown in the northeastern regions of Brazil and is popularly known as "sambacaitá" or "canudinho". It is extensively used in folk medicine to treat inflammatory conditions, bacterial infections, pain, and cancer. MATERIALS AND METHODS: Hyptis pectinata essential oil (EO, 10, 30, and 100mg/kg, p.o.) and the reference drugs morphine (5mg/kg, p.o.) and acetylsalicylic acid (ASA, 200mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and hot plate) or inflammation (formalin-induced licking response and the subcutaneous air-pouch model). To elucidate the EO's mechanism of action, animals were pre-treated with the opioid receptor antagonist naloxone (1mg/kg, i.p.), the cholinergic antagonist atropine (1mg/kg, i.p.), or l-nitro arginine methyl ester (l-NAME, 3mg/kg, i.p.) 30 min prior to the oral administration of the EO. RESULTS: The EO significantly inhibited the number of writhings and the time the animals spent licking their formalin-injected paws (second phase). The EO, at doses of 30 and 100mg/kg, increased baseline measurements and area under the curve measurements in the hot plate model, respectively. The administration of naloxone reversed the antinociceptive effect of the EO in the hot plate model. l-NAME significantly reversed the effects of the EO in the contortions and hot plate models. Atropine completely reversed the antinociceptive activity of the EO in all models. Additionally, the EO inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, exudate volume, protein concentration, and inflammatory mediators (nitric oxide, prostaglandin E2, IL-6, and TNF-α) produced in the pouch. CONCLUSIONS: Our results indicate that the Hyptis pectinata essential oil exhibits antinociceptive effects, likely mediated by opioid and cholinergic receptors, and anti-inflammatory activity through the inhibition of nitric oxide and PGE2 production.

Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol.

We examined the antioxidant properties in vitro and the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidation in vitro. In mice, when evaluated against acetic acid-induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%, p < 0.001) and glutamate (46.4, 61.4 and 97.9%, p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro-oxidant states.

A study of the larvicidal activity of two Croton species from northeastern Brazil against Aedes aegypti.

The essential oils of Croton heliotropiifolius Kunth (Euphorbiaceae) and Croton pulegiodorus Baill. were selected for larvicidal evaluation against Aedes aegypti L. (Diptera: Culicidae) and studied qualitatively and quantitatively by GC and GC-MS. Sixty-one compounds representing 92.03% (C. heliotropiifolius) and 85.68% (C. pulegiodorus) of the essential oils, respectively, have been identified. The major components of C. heliotropiifolius essential oil were identified as beta-caryophyllene (35.82%), bicyclogermacrene (19.98%), and germacrene-D (11.85%). The major components in C. pulegiodorus essential oil were identified as beta-caryophyllene (20.96%), bicyclogermacrene (16.89%), germacrene-D (10.55%), tau-cadinol (4.56%), and beta-copaen-4-alpha-ol (4.35%). The essential oil of C. pulegiodorus (LC50 159 ppm) was more effective against Ae. aegypti than that of C. heliotropiifolius (LC50 544 ppm). In order to verify whether the major compound of both essential oils is the active principle responsible for the larvicidal activity, beta-caryophyllene was purchased and its larvicidal potential was further evaluated. However, beta-caryophyllene (LC50 1038 ppm) showed weak larvicidal potency. Results of larvicidal evaluation suggest the existence of a synergistic effect of minor components in the essential oils.

Larvicidal activity of para-benzoquinones.

Plant products may be alternative sources of mosquito larval control agents, since they constitute a rich source of bioactive compounds that are biodegradable into nontoxic products. It has been reported that quinones and derivatives present toxic activity against mosquito larvae Aedes aegypti. Therefore, these facts led us to investigate the larvicidal potential of six structurally related para-benzoquinones against A. aegypti L. (Culicidae) larvae, the vector of dengue fever. All the para-benzoquinones were found to have larvicidal effect. The unsubstituted para-benzoquinone was the compound that exhibited the lowest potency, while 2-isopropyl-para-benzoquinone was the most bioactive. In general, the presence of alkyl groups results in more potent compounds. In addition, the number, position, and size of these groups modulate the potency of the compounds. The experimental results showed that by appropriate structural modification of para-benzoquinones, it may be possible to develop novel insecticidal compounds with potential use to control A. aegypti population.

Toxic effects on and structure-toxicity relationships of phenylpropanoids, terpenes, and related compounds in Aedes aegypti larvae.

In the search for toxic compounds against Aedes aegypti L. (Diptera: Culicidae) larvae, a collection of commercially available aromatic and aliphatic diversely substituted compounds were selected and evaluated. p-Cymene exhibited the highest larvicidal potency LC50 = 51 ppm, whereas 1,8-cineole exhibited the lowest activity value LC50 = 1419 ppm. To aid future work on the search for larvicidal compounds, the structure-toxicity relationships of this collection have been evaluated. The presence of lipophilic groups results in an overall increase in potency. In general, the presence of hydroxyl groups resulted in less potent compounds. However, methylation of such hydroxyls led to an overall increase in potency. The most potent compounds showed comparably good larvicidal activity in A. aegypti larvae as other terpenes, which we assume to be the result of the increased lipophilicity.

Evidence of the mechanism of action of Erythrina velutina Willd (Fabaceae) leaves aqueous extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina velutina is traditionally used for sleepiness, convulsions and nervous system excitation in Brazil. Although central effects have been reported for Erythrina velutina, little is known about its mechanism of action. AIM OF THE STUDY: To investigate the pharmacological evidences of mechanism of action of Erythrina velutina leaves aqueous extract (AE). MATERIALS AND METHODS: Terminal segments of the guinea-pig ileum (n=5-8) were mounted in an organ bath and isotonic contractions were recorded. Phytochemical screening was carried out on AE. RESULTS: AE (0.025-2.50 mg/ml) produced contractile response in the guinea-pig ileum, yielding typical concentration-response curves (EC50=0.63 mg/ml). Electrically evoked contractions were significantly increased in the presence of AE. AE-elicited contractions were significantly reduced by bicuculline, tetrodotoxin, atropine, verapamil or incubation in low calcium-high potassium solution. Atropine along with verapamil abolished AE contractile response. Alkaloids, catechins, steroids, flavonols, flavononols, flavonoids, phenols, saponins, tannins, triterpenoids, and xanthones were detected in AE. CONCLUSIONS: AE contains important constituents for pharmacological activities. AE-induced contractions seem to involve GABAA receptor activation, acetylcholine release, muscarinic receptor activation, augmentation of Ca2+ entry through L-type calcium channels, and calcium release from the intracellular stores. These findings provide further support for Erythrina velutina traditional uses.