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The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic acid derivative and three flavokawains...
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... 2 was a dark yellow solid. The HRESIMS analysis indicated the presence of a quasi-molecular ion peak at m/z 357.2060, corresponding to the formula C 22 (Table 1) (Table 1). Singlet signals at δ1.65 (3H), 2.26 (3H), 1.65 (3H) and 1.57 (3H) were assigned to methyl groups linked to sp 2 carbon atoms. ...
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... 2 was a dark yellow solid. The HRESIMS analysis indicated the presence of a quasi-molecular ion peak at m/z 357.2060, corresponding to the formula C 22 (Table 1) (Table 1). Singlet signals at δ1.65 (3H), 2.26 (3H), 1.65 (3H) and 1.57 (3H) were assigned to methyl groups linked to sp 2 carbon atoms. ...
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... 164.10, 127.70, 136.82, 124.30 and 131.57 corresponding to three double bonds, δ 42.11, 26.81, 39.79, 26.30 were assigned to methylene groups and δ 25. 91, 20.57, 16.28 and 17.80 to methyl groups of the farnesyl group (Table 1). A comparison of data in the literature [14] with that of compound 2 corroborated the structure this compound as 4-hydroxy-3-(3,7,11-trimethyldodeca- 2,5,10-trienyl)benzoic acid (Figure 1). ...
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... molluscicidal and ovicidal activities of compounds 1 and 2 were evaluated against B. glabrata. The molluscicidal and ovicidal activities of commercially available analogs of the benzoic acid derivative, hydroquinone and p-hydroxybenzoic acid, and the two chalcones 3 and 4 isolated from P. cumanense and P. gaudichaudianum, were also evaluated ( Table 2, Supplementary Table S1). Compound 2 was potent against adult snails among the natural products tested (LC 50 7.28 µg/mL) ( Table 2). ...
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... 2 was potent against adult snails among the natural products tested (LC 50 7.28 µg/mL) ( Table 2). A concentration of 12 µg/mL resulted in 100% dead animals after 24 h of exposure (Supplementary Table S1). This benzoic acid derivative was significantly more potent compared with p-hydroxybenzoic acid (LC 50 1302.91 ...
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... a simple quinone 6 was the most active (LC 50 3.15 µg/mL) among the tested compounds. The quinone was also active against the embryonic stages of B. glabrata, however, the benzoic acid and compound 1 did not have any activity against these stages (Table 2) (Supplementary Table S1). A concentration of 9 µg/mL hydroquinone resulted in 100% dead adult animals after 24 h of exposure. ...
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... compound with the most potent activity was 2',4',6'-trihydroxy- dihydrochalcone (3), which was active against all life stages of the snail. This compound was more active in the adults (LC 50 5.35 µg/mL) ( Table 2, Supplementary Table S1), but in the embryonic stages caused a delay in development; after 7 days all the embryos had not completed development and remained in the eggs. The eggs were examined daily and regardless of heart beat detection did not emerge from the eggs. ...
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... with 10-18 mm of shell diameter were exposed to P. diospyrifolium extract and isolated compounds (Table 1, Supplementary Table S1) at concentrations less than 40 mg/mL for 24 h at 24 °C ± 2 °C. After exposure, the snails were washed, observed daily for 7 days, and the death rate was recorded [19]. ...
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... egg masses at the blastula, gastrula, trocophore and veliger stages [20] were exposed to isolated compounds at concentrations less than 20 mg/mL for 24 h to determine the LC 90 and LC 50 values. The number of snail embryos to each concentration is indicated in Supplementary Table S1. Following the exposure, the egg masses were washed with dechlorinated water and Petri dishes containing egg masses were kept within climatic chambers with a controlled temperature (25 °C ± 1 °C). ...
Citations
... According to Rapado et al. (2014), some crude extracts from plants of the Piperaceae family proved to be effective in controlling the mollusk intermediate hosts of schistosomiasis, due to this, a deeper investigation was initiated using the genus, Piper. From the crude extract of the leaves of Piper diospyrifolium, two compounds were isolated, Flavokawain A and Benzoic acid (4-hydroxy-3-(3,7,11-trimethyldodeca -2,5,10-trienyl)). ...
... The biological tests carried out by Rapado et al. (2014) were carried out according to the methodology by WHO/1983. In the bioassay ten adult mollusks with a shell diameter between 10-18 mm were used, and were exposed to the isolated compounds within 24 hours, being checked for seven days. ...
Schistosomiasis is a neglected tropical disease caused by parasitic worms of several species of the genus Schistosoma. Transmission occurs by parasitic larvae that stay in freshwater snails of the genus Biomphalaria. Thus, the search for new products that are biodegradable has increased the interest in products of plant origin. The aim of this article is to review the isolated substances from natural products that showed molluscicidal activity against the species Biomphalaria glabrata in order to reevaluate the most promising prototypes and update the progress of research to obtain a new molluscicide. We perform searches using scientific databases, such as Scientific Electronic Library Online (SciELO), Google schoolar, PUBMED, Web of Science and Latin American and Caribbean Literature on Health Sciences (LILACS). From 2000 to 2022, using the keywords “isolated substances”, “molluscicidal activity” and “Biomphalaria glabrata”. In the present study, it was possible to observe 19 promising molluscicidal molecules with a lethal concentration below 20 µg/mL. Of these promising isolates, only 5 isolates had the CL90 calculated and within the value recommended by WHO: Benzoic acid, 2',4',6'-Trihydroxydihydrochalcone, Divaricatic acid, Piplartine and 2-hydroxy-1,4-naphthoquinone (Lapachol). We conclude that beyond a few results in the area, the researches don’t follow the methodological pattern (exposure time and measure units, toxicity test), in this way, as they don’t follow a pattern on the result’s exposure (LC), not following, in sum, the recommended by WHO.
... cumanense, including mainly prenylated benzoic acid derivatives, terpenes, and flavonoids [27][28][29]32]. The inhibitory effect on digestive enzymes of P. cumanense and its constituents has not been reported. ...
Digestive enzymes are currently considered important therapeutic targets for the treatment of obesity and some associated metabolic diseases, such as type 2 diabetes. Piper cumanense is a species characterized by the presence of bioactive constituents, particularly prenylated benzoic acid derivatives. In this study, the inhibitory potential of chemical constituents from P. cumanense and some synthesized compounds was determined on digestive enzymes (pancreatic lipase (PL) and α-glucosidase (AG)). The methodology included isolating and identifying secondary metabolites from P. cumanense, synthesizing some analogs, and a molecular docking study. The chemical study allowed the isolation of four prenylated benzoic acid derivatives (1–4). Four analogs (5–8) were synthesized. Seven compounds were found to significantly inhibit the catalytic activity of PL with IC50 values between 28.32 and 55.8 µM. On the other hand, only two compounds (6 and 7) were active as inhibitors of AG with IC50 values lower than 155 µM, standing out as the potential multitarget of these chromane compounds. Enzyme kinetics and molecular docking studies showed that the bioactive compounds mainly interact with amino acids other than those of the catalytic site in both PL and AG. This work constitutes the first report on the antidiabetic and antiobesity potential of substances derived from P. cumanense.
... environment contamination, the excessive use of synthetic insecticides also affects other non-target organisms (Carmo et al. 2017;Haddi et al. 2017). Therefore, the investigation of green sources containing bioactive compounds as botanicals with insecticidal properties represents an important alternative for controlling agent (Rapado et al. 2014;Chandrasekaran et al. 2017). ...
Diseases transmitted by the mosquito Aedes aegypti, Culicidae, are a serious public health problem worldwide, especially because of the increasing resistance to synthetic insecticides. Volatile oils are botanicals with interesting multi-target properties, but with reduced applications due to its volatility and water solubility. For this reason, nanoemulsions containing volatile oils are an important alternative for the mosquito control. The volatile oil of leaves Piper alatipetiolatum Yunck., Piperaceae, was
characterized mostly by sesquiterpenes, such as ishwarone (78.6%), ishwarol B (8.2%), β-elemene (6.9%), selin-11-en-4α-ol (2.9%), and ishwarane (2.4%). The volatile oil showed lower ovicidal activity (19 to 100%), larvicidal activity (LC50 33.74 ppm), and pupicidal activity (LC50 65.06 ppm) as compared with its nanoemulsion that presented higher ovicidal activity (47.7 to 100%), larvicidal activity (LC50 6.37 ppm), and pupicidal activity (LC50 9.33 ppm) against Ae. aegypti. The volatile oil nanoemulsion was characterized with approximately spherical morphology, with an average size of 316 ± 8 nm, PDI of 0.44
± 0.01, zeta potential of − 8.5 ± 0.1 mV, and pH of 5.3 ± 0.1. These results indicated that the nanoemulsion containing the encapsulated volatile oil was effective to interrupt the development of immature forms of Ae. aegypti and represents an efficient alternative tool to control this vector, contributing to vector control of dengue and other related diseases.
... The structures of all compounds were characterized by comparison with the literature. Their structures were identified as alpiblepharin A (1), flavokawain A (2) [12], 2', 6'-dihydroxy-4'metoxychalcone (3) [13], nevadensin (4) [14], apigenin (5) [15], apigetrin (6) [15], cynaroside (7) [16], rutin (8) [17], and polydatin (9) [18]. Compound 1 was obtained as a white powder, and its molecular formula C15H26O, determined by HR-ESI-MS at m/z 245.1853 [M + Na] + (calcd for C15H26ONa, 245.1881). ...
... It was previously reported to have been isolated from Piper species such as Piper diospyrifolium. 33 The present study reports the isolation of flavokawain A for the first time from Peperomia species. Molecular ion mass peak of this compound appeared at m/z [M + H] + 315.07, corresponding to molecular formula of C 18 H 18 O 5 , and base peak at 299 due to the loss of CH 3 . ...
... The NMR data were compared to the literature. 33,34 Three single peaks were observed at δ H 3.88−3.97 ppm for the assignment of three methoxy groups and was confirmed by the 13 C NMR at δ C 55.6−55.8 ...
... Peaks at δ C 92.4 and 97.8 ppm confirmed the presence of protons on benzene ring that has been substituted with methoxy or hydroxyl groups. 33 3.4.4. Peperomin A and N,N′-Diphenethyloxamide. Peperomin A (Figure 4) is a rare occurrence, and it has been previously reported to be the most common phytochemical constituent of Peperomia species. ...
Bioassay-guided isolation protocol was performed on petroleum
ether extract of Peperomia blanda (Jacq.) Kunth using column chromatographic
techniques. Five compounds were isolated and their structures were elucidated
via one-dimensional (1D) and two-dimensional (2D) NMR, gas chromatography
mass sectroscopy (GCMS), liquid chromatography mass spectroscopy (LCMS),
and ultraviolet (UV) and infrared (IR) analyses. Dindygulerione E (a new
compound), and two compounds isolated from P. blanda for the first time
namely, dindygulerione A and flavokawain Aare reported herein. Antimicrobial
activity was screened against selected pathogenic microbes, and minimum
inhibitory concentrations (MIC) were recorded within the range of 62−250 μg/
mL. Assessment of the pharmacotherapeutic potential has also been done for the
isolated compounds, using the Prediction of Activity spectra for Substances
(PASS) software, and different activities of compounds were predicted.
Molecular docking, molecular dynamics simulation and molecular mechanics/
Poisson−Boltzmann Surface Area (MM-PBSA) calculations have proposed the binding affinity of these compounds toward
methylthioadenosine phosphorylase enzyme, which may explain their inhibitory actions.
... Idioblasts are present in all parts of P. aduncum plants, mostly in the leaves (Lakshmia & Naidu 2010, Marinho et al. 2011, Gogosz et al. 2012, Nakamura et al. 2015, Santos et al. 2018, which are the source for the highest amounts of essential oil. These secondary metabolism compounds are targeted by the chemical industry and present multiple biological effects exploited as insecticides, fungicides, molluscicides, acaricides, bactericides and larvicides, with the advantage of being biodegradable products (Zacaroni et al. 2009, Costa et al. 2010, Pino et al. 2011, Piton et al. 2014, Rapado et al. 2014, Santos & Siviero 2015, Pinto et al. 2016. ...
The growing of Piper aduncum for essential oil extraction
has increased, but there is a lack of basic information about its
management and cultivation, which allows the productivity and
quality of the oil, in order to attend the market demands. This
study aimed to evaluate the relation between the production
of essential oils from P. aduncum and soil water pressure
heads (20 kPa, 40 kPa, 60 kPa, 100 kPa and non-irrigated). The
assessment comprised the quantification of idioblasts and the
production of essential oil extracted from leaves of cultivated
plants. The variation in the soil water pressure head alters the
amount of idioblasts in P. aduncum leaves, with impacts on the
essential oil production. A soil water pressure head range of
20-60 kPa is sufficient for this species to express the highest
amount of idioblasts and the highest level of essential oil
production. The species adapts itself to different water availability
conditions in the soil. Under stress conditions, due to water deficit
or excess, the production of essential oil is reduced.
... The chemistry of Piper species is characterized by the production classes of compounds common to many plant species like phenylpropanoids, lignans, neolignans, and flavonoids (Parmar et al., 1998). Besides, there are somewhat specific classes of compounds such as aliphatic and aromatic amides (Parmar et al., 1998;Marques et al., 2007;Maciel et al., 2016;Shi et al., 2017), prenylated benzoic acids, chromenes (Terreaux et al., 1998;Rapado et al., 2014), kavalactones (Dharmaratne et al., 2002), and protoflavonoids . ...
... Previous phytochemical studies of P. diospyrifolium leaves have led to the isolation of a farnesyl-benzoic acid derivative with molluscicidal effects (LC 50 7.28 μg/mL) against adults of Biomphalaria glabrata (Rapado et al., 2014). A di-prenylated benzoic acid was assessed against Mycobacterium tuberculosis and shown weak activity (Scodro et al., 2015). ...
As part of our continuing phytochemical survey on Piper species, three previously undescribed alkenylphenols were isolated and characterized, including 4-[(3′E)-tetradec-3′-en-1-yl] phenol (1) and 4-[(2′E,4′E)-heptadeca-2′,4′-dien-1-yl] phenol (3) from P. diospyrifolium and 4-[(3′E)-hexadec-3′-en-1-yl] phenol (2) from P. dilatatum. The structures of the compounds were determined based on spectroscopic analyses including 1D and 2D NMR and high-resolution mass spectrometry.
... These phenylpropanoids may also act as precursors for the chromenes, flavokawains and flavonoids reported in this species. 26,28,29 With respect to isoquinolinic alkaloids, the genes identified are involved in the early steps of their biosynthesis involving dopamine production ( Figure S3, Supplementary Information). Although there are no reports of the occurrence of these compounds in Piper gaudichaudianum, two aporphinoid alkaloids, cepharadione A and piperolactam E, were isolated from Piper caninum and Piper taiwanense, respectively. ...
Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyran, as its major component. Interestingly, this trypanocidal compound occurs as a racemic mixture. Herein, transcriptomic investigations of Piper gaudichaudianum using the RNA-seq approach are reported, and from the analysis of the transcripts expressed it was possible to propose a complete biosynthetic pathway for the production of gaudichaudianic acid, including the steps that originate its precursor, p-hydroxybenzoic acid. Peperomia obtusifolia (L.) A. Dietr. (Piperaceae) also accumulates racemic benzopyrans, however, its chromanes originate from the polyketide pathway, while the chromenes from Piper derives from the shikimate pathway. Recent transcriptomic and proteomic studies of the former species did not identify polyketide synthases involved in the production of the benzopyran moiety, but revealed the expression of tocopherol cyclase, which may be responsible for the cyclization of the 3,4-dihydro-2H-pyran ring. The analysis of the enzymes involved in the secondary metabolism of Piper gaudichaudianum and the comparison with the data previously obtained from Peperomia obtusifolia can provide valuable information on how these compounds are biosynthesized.
... Currently molluscicides, such as the commercially available niclosamide-based Bayluscide, are effectively employed in schistosomiasis control programs; however the problems of resistance and toxicity to other organisms means that the search for alternative, more selective, compounds is on-going. The capacity of nuclear receptors to bind small ligands, including exogenous substances such as natural products and synthetic chemicals, makes them potential targets for molluscicides [120]. Biomphalaria glabrata as a model organism There is a long tradition in biology of examining biochemical processes in simplified models to elucidate mechanisms in more complex organisms. ...
Nuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates , however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates , such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail en-docrine systems are fundamentally different.
