Grandisin caused morphological changes larval and toxicity on Aedes aegypti

Leite, Ana Carolina C. F.; Kato, Massuo Jorge; Soares, Renata Oliveira; Guimarães, Anthony Érico; Santos-Mallet, Jacenir Reis dos; Cabral, Marise M. O.

doi:10.1590/s0102-695x2012005000016

Cited by 17 publications

(16 citation statements)

References 15 publications

(3 reference statements)

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“…The bioassays were carried out using eggs that were placed in a receptacle containing mineral water with fish food (0.3 mg/larva) (Alcon Guppy) for hatching [9,25]. All experiments were carried out on third instar (L3) larvae (F1-F5) in triplicate with three repetitions, to determine the effect of the neolignan.…”

Section: Methodsmentioning

confidence: 99%

Burchellin: study of bioactivity against Aedes aegypti

et al. 2014

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BackgroundThe dengue mosquito Aedes aegypti Linnaeus, 1762 is a widespread insect pest of serious medical importance. Since no effective vaccine is available for treating dengue, the eradication or control of the main mosquito vector is regarded as essential. Since conventional insecticides have limited success, plants may be an alternative source of larvicidal agents, since they contain a rich source of bioactive chemicals. The aim of this study was to evaluate the larvicidal activity of the neolignan burchellin isolated from Ocotea cymbarum (Lauraceae), a plant from the Amazon region, against third instar larvae of A. aegypti.MethodsBurchellin obtained from O. cymbarum was analyzed. The inhibitory activity against A. aegypti eggs and larvae and histological changes in the digestive system of treated L3 larvae were evaluated. In addition, nitric oxide synthase activity and nitric oxide levels were determined, and cytotoxicity bioassays performed.ResultsThe data showed that burchellin interfered with the development cycle of the mosquito, where its strongest toxic effect was 100% mortality in larvae (L3) at concentrations ≥ 30 ppm. This compound did not show target cell toxicity in peritoneal macrophages from BALB/c mice, and proved to have molecular stability when dissolved in water. The L3 and L4 larvae treated with the compound showed cellular destruction and disorganization, cell spacing, and vacuolization of epithelial cells in small regions of the midgut.ConclusionThe neolignan burchellin proved to be a strong candidate for a natural, safe and stable phytolarvicidal to be used in population control of A. aegypti.

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Section: Methodsmentioning

confidence: 99%

Burchellin: study of bioactivity against Aedes aegypti

et al. 2014

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“…[2,3] (À)-grandisin ( Figure 1), a tetrahydrofuran lignan isolated from Piperaceae, Lauraceae, Myristicaceae and Schisandraceae species, [4][5][6][7] is considered as a novel drug candidate. This compound has displayed several biological activities, such as trypanocidal activity against the trypomastigote form of Trypanossoma cruzi, [8][9][10][11] larvicidal activity against the mosquito Aedes aegypti, [12,13] and antinociceptive and anti-inflammatory activities. [14] More recently, many studies have evaluated its cytotoxic and antitumor activities, suggesting (À)grandisin as a potential anticancer agent.…”

Section: Introductionmentioning

confidence: 99%

“…[14] More recently, many studies have evaluated its cytotoxic and antitumor activities, suggesting (À)grandisin as a potential anticancer agent. [13][14][15][16][17] To date, many investigations have been performed to explore (À)-grandisin metabolism using several in vitro models, such as fungi, [17,18] insects, [19] pig ceca, Jacobsen catalysts, [20] and rat hepatic microsomes. [21] Considering that the liver is the major drug-metabolizing organ, liver-derived systems are the most suitable for metabolic studies.…”

Section: Introductionmentioning

confidence: 99%

In vitro metabolism of the lignan (−)‐grandisin, an anticancer drug candidate, by human liver microsomes

Barth

Habenschus

Moreira

et al. 2015

Drug Testing and Analysis

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(-)-grandisin is a tetrahydrofuran lignan that displays important biological properties, such as trypanocidal, anti-inflammatory, cytotoxic, and antitumor activities, suggesting its utility as a potential drug candidate. One important step in drug development is metabolic characterization and metabolite identification. To perform a biotransformation study of (-)-grandisin and to determine its kinetic properties in humans, a high performance liquid chromatography (HPLC) method was developed and validated. After HPLC method validation, the kinetic properties of (-)-grandisin were determined. (-)-grandisin metabolism obeyed Michaelis-Menten kinetics. The maximal reaction rate (Vmax ) was 3.96 ± 0.18 µmol/mg protein/h, and the Michaelis-Menten constant (Km ) was 8.23 ± 0.99 μM. In addition, the structures of the metabolites derived from (-)-grandisin were characterized via gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analysis. Four metabolites, 4-O-demethylgrandisin, 3-O-demethylgrandisin, 4,4'-di-O-demethylgrandisin, and a metabolite that may correspond to either 3,4-di-O-demethylgrandisin or 3,5-di-O-demethylgrandisin, were detected. CYP2C9 isoform was the main responsible for the formation of the metabolites. These metabolites have not been previously described, demonstrating the necessity of assessing (-)-grandisin metabolism using human-derived materials.

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“…Amides (27) and lignans (3) are the most cited active chemical classes found in Piper species with larvicidal properties against dengue vector A. aegypti ( Table 2). These are the chemicals most often found in Piper species, especially in P. nigrum, the most studied species from Piperaceae family (Rahman 2012, Siddiqui et al 2003, 2005, Leite et al 2012, Simas et al 2004, Solis et al 2005, Lee 2005, Da Silva et al 2011). …”

Section: Larvicidal Potential Of Isolated Metabolites From Piper Speciesmentioning

confidence: 99%

“…Grandisin caused third instar A. aegypti larvae mortality with LC50 value of 150 µg/mL. Larvae treated with grandisin showed an LC50 value of 50 µg/mL and underwent morphological body changes, with intense tissue destruction and cell disorganization (Leite et al 2012). The treatment of L1 larvae of A. aegypti with grandisin presented 100% larval mortality at a concentration of 100 μg/mL (Cabral et al 2009).…”

Section: Larvicidal Potential Of Isolated Metabolites From Piper Speciesmentioning

confidence: 99%

Active metabolites of the genus Piper against Aedes aegypti: natural alternative sources for dengue vector control

Marques

Kaplan²

2014

Univ. Sci.

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The mosquito, Aedes aegypti, is the principal vector of the viruses responsible for dengue and dengue hemorrhagic fevers. The mosquito is widespread throughout tropical and sub-tropical regions; its prevalence makes dengue one of the most important mosquito-borne viral diseases in the world occurring annually in more than 100 endemic countries. Because blood is essential to their development cycle, the Aedes species maintains a close association with humans and their dwellings. Fittingly, the most widely adopted strategy to decrease the incidence of these diseases is the control of the mosquito larvae population. The emergence of insecticide-resistant mosquitoes has amplified the interest in finding natural products effective against Aedes aegypti adults, as well as larvae. Plantderived compounds have played an important role in the discovery of new active entities for vector management as they are safer and have lower toxicity to humans in comparison to conventional insecticides. This review assesses a naturally occurring plant matrix and pure compounds of the Piper species, which have been shown to be active against Aedes aegypti.

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Grandisin caused morphological changes larval and toxicity on Aedes aegypti

Cited by 17 publications

References 15 publications

Burchellin: study of bioactivity against Aedes aegypti

Burchellin: study of bioactivity against Aedes aegypti

In vitro metabolism of the lignan (−)‐grandisin, an anticancer drug candidate, by human liver microsomes

Active metabolites of the genus Piper against Aedes aegypti: natural alternative sources for dengue vector control

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