Design, Synthesis, Characterization, and Molluscicidal Activity Screening of New Nicotinonitrile Derivatives against Land Snails, M. cartusiana.

A new series of nicotinonitrile derivatives 2-7 was designed and synthesized from the starting material (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (1) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2-7 were characterized based on FTIR, 1H-NMR, and 13C-APT NMR spectra as well as elemental microanalyses. The target compounds 2-7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2, 4a, and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a,b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a,b could be adequate molluscicidal molecules against M. cartusiana land snails.

Molluscicidal and cercaricidal activities of the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants: Implications for the control of schistosomiasis.

Schistosomiasis is one of the most important tropical diseases. A fundamental strategy to control its spread is the use of natural products against its vectors, which are snails of the genus Biomphalaria. The present study evaluated the chemical composition, the molluscicidal and cercaricidal effects, and the ecotoxicity of the essential oil from the aerial parts of Dysphania ambrosioides (L.) Mosyakin & Clemants (DAEO). The essential oil was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Molluscicidal and cercaricidal activities were determined by the immersion method. Environmental toxicity was assessed from bioassays using Artemia salina larvae and Danio rerio fish. DAEO presented a 0.8% yield. The GC-MS analysis revealed the predominance of hydrocarbon monoterpenes in the oil. A total of 32 constituents was identified, with α-terpinene (50.69%) being the major compound, followed by p-cymene (13.27%) and ascaridole (10.26%). DAEO was active against adult Biomphalaria glabrata snails and demonstrated lethal effect against Schistosoma mansoni cercariae, with LC50 values of 25.2 (22.7-27.8) and 62.4 (61.8-62.9) µg/mL, respectively. Regarding toxicity to non-target aquatic organisms, the oil showed LC50 values of 86.9 (84.7-87.6) and 18.6 µg/mL (15.5-22.8) for A. salina and D. rerio, respectively. DAEO proved to be a promising natural product for the control of schistosomiasis, acting on both the vectors and the etiological agent of the disease. However, the use of the oil is safer in transmission sites where there are no non-target organisms, as it has showed toxicity to D. rerio fish.

Application of nanotized formulation in the control of snail intermediate hosts of schistosomes.

Schistosomiasis continues to pose significant public health problems in many developing countries. Mass drug administration (MDA) is the most adopted control option but there is increasing evidence for the development of praziquantel-resistant Schistosoma strains. This shortcoming has necessitated the search for other effective methods for the control of schistosomiasis. The breaking of Schistosoma transmission cycles through the application of molluscicides into snail infested freshwater bodies has yielded positive outcomes when integrated with MDA in some countries. However, few of such effective molluscicides are currently available, and where available, their application is restricted due to toxicity concerns. Some nanotized particles with molluscicidal activities against the different stages of snail intermediate hosts of schistosomes have been reported. Importantly, the curcumin-nisin nanoparticle synthesized by our group was very effective and it showed no significant toxicity in a mouse model and brine shrimps. This, therefore, offers the possibility of developing a molluscicide that is not only safe for man but also is environmentally friendly. This paper reviews nanoparticles with molluscicidal potential. The methods of their formulation, activities, probable mechanisms of actions, and their toxicity profiles are discussed. More research should be made in this field as it offers great potential for the development of new molluscicides.

Lantana camara Essential Oils from Vietnam: Chemical Composition, Molluscicidal, and Mosquito Larvicidal Activity.

Lantana camara is a troublesome invasive plant introduced to many tropical regions, including Southeast Asia. However, the plant does hold promise as a source of essential oils that may be explored for potential use. Fresh water snails such as Pomacea canaliculata, Gyraulus convexiusculus, and Tarebia granifera can be problematic agricultural pests as well as hosts for parasitic worms. Aedes and Culex mosquitoes are notorious vectors of numerous viral pathogens. Control of these vectors is of utmost importance. In this work, the essential oil compositions, molluscicidal, and mosquito larvicidal activities of four collections of L. camara from north-central Vietnam have been investigated. The sesquiterpene-rich L. camara essential oils showed wide variation in their compositions, not only compared to essential oils from other geographical locations (at least six possible chemotypes), but also between the four samples from Vietnam. L. camara essential oils showed molluscicidal activities comparable to the positive control, tea saponin, as well as other botanical agents. The median lethal concentrations (LC50 ) against the snails were 23.6-40.2 µg/mL (P. canaliculata), 7.9-29.6 µg/mL (G. convexiusculus), and 15.0-29.6 µg/mL (T. granifera). The essential oils showed good mosquito larvicidal activities with 24-h LC50 values of 15.1-29.0 µg/mL, 26.4-53.8 µg/mL, and 20.8-59.3 µg/mL against Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus, respectively. The essential oils were more toxic to snails and mosquito larvae than they were to the non-target water bug, Diplonychus rusticus (24-h LC50 =103.7-162.5 µg/mL). Sesquiterpene components of the essential oils may be acting as acetylcholinesterase (AChE) inhibitors. These results suggest that the invasive plant, L. camara, may be a renewable botanical pesticidal agent.

[Study on the factors affecting the degradation of niclosamide in the soil].

OBJECTIVE: To investigate the factors affecting the degradation of niclosamide in the soil, so as to provide the evidence for the assessment of the environmental safety in the field snail control with niclosamide. METHODS: A high performance liquid chromatography was established for the determination of niclosamide in the field. Then, the degradation of niclosamide was investigated in soils with different moistures (10%, 30%, 50%, 70% and 90%), temperatures [(15 ± 1), (25 ± 1), (35 ± 1) °C], initial concentrations (1, 5, 10 mg/kg) and in sterilized and non-sterilized soils. In addition, the degradation of niclosamide was fitted with the first-order kinetics equation, and the degradation half-life was calculated. RESULTS: The niclosamide residues gradually decreased over time in soils with different moistures, and a higher rate of degradation was seen in soils with a higher moisture. The degradation half-life of niclosamide reduced from 4.258 d in the soil with a 10% moisture to 2.412 d in the soil with a 90% moisture. The niclosamide residues gradually decreased over time in soils with different temperatures, and a higher rate of degradation was seen in soils with a higher temperature. The degradation half-life of niclosamide reduced from 4.398 d in the soil with a temperature of (15 ± 1) °C to 2.828 d in the soil with a temperature of (35 ± 1) °C. The degradation half-lives of niclosamide were 3.212, 3.333 d and 3.448 d in soils containing niclosamide at initial concentrations of 1, 5 mg/kg and 10 mg/kg, and > 30 d and 3.273 d in sterilized and non-sterilized soils. Multiple linear regression analysis revealed that soil microorganisms (P = 0.010), moisture (P = 0.000) and temperature (P = 0.002) affected the half-life of niclosamide degradation. CONCLUSIONS: The degradation of niclosamide in soils fits the first-order kinetics equation, and presence of microorganisms, a high temperature and high moisture may accelerate the degradation of niclosamide in the soil.

Molluscicidal activity of polyvinylpyrrolidone (PVP)-functionalized silver nanoparticles to Biomphalaria glabrata: Implications for control of intermediate host snail of Schistosoma mansoni.

Silver nanoparticles (Ag NPs) have been applied in several commercial products due to their antimicrobial properties, while their molluscicide properties, mode of action and toxicity to snail species remain unclear. In this study, the comparative toxicity of polyvinylpyrrolidone (PVP)-functionalized Ag NPs and their dissolved counterpart (Ag ions) was analyzed during the early developmental stages of the freshwater snail Biomphalaria glabrata, intermediate host of Schistosoma mansoni. Ag NPs were synthesized and characterized by multiple techniques, and the snail embryotoxicity was analyzed in terms of mortality, hatching, developmental stages and morphological alterations, while the acute toxicity to newly-hatched snails was analyzed by mortality and behavioral impairments. Results showed that both Ag forms induced mortality, hatching delay and morphological alterations (especially hydropic abnormalities) in snail embryos in a concentration and exposure time dependent patterns. Ag NPs showed low embryotoxic effects and similar toxicity for newly-hatched snails when compared to their dissolved counterparts, indicating that the nanotoxicity was dependent of snail developmental stages. The knowledge about the Ag NP toxicity to different early development stages of B. glabrata contributes to its potential use as molluscicide and control of neglected tropical diseases, including schistosomiasis.

Toxicological effects of Ramalina aspera (lichen) on Biomphalaria glabrata snails and Schistosoma mansoni cercariae.

In this study, the molluscicidal activities against Biomphalaria glabrata and cercaricidal activities against Schistosoma mansoni of the ether extract of Ramalina aspera were evaluated. Additionally, toxicity parameters were evaluated at sublethal doses in terms of the influence of the extract on the fertility and fecundity of snails, as well as morphological alterations and quantification of their immunological cells. A test with Artemia salina was also carried out, in order to verify the environmental toxicity of the compound. The ether extract of R. aspera, in which divaricatic acid was identified as the major compound, demonstrated molluscicidal activity at low concentrations against both embryos (LC90 of 22.78, 24.23, 16.63 and 16.03 µg mL-1 for the gastrula, blastula, trochophore and veliger, respectively) and against adult snails (LC90 of 8.66 µg mL-1), after 24 h of exposure. At the sublethal doses, it was possible to observe a decrease in fecundity and quantitative and morphological changes in the defense cells of the exposed snails. In addition, the extract of R. aspera showed a cercaricidal effect on S. mansoni from the concentration of 5.0 µg mL-1, while showing low toxicity to Artemia salina. The ether extract of R. aspera demonstrated effective molluscicidal activity on embryos and adult snails of the species B. glabrata, cercariae of S. mansoni, and presenting low toxicity on Artemia salina. In this way, it could be considered a promising compound in the development of future molluscicidal and cercaricidal agents, thus helping to combat schistosomiasis.

[Molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands].

OBJECTIVE: To evaluate the molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands. METHODS: The molluscicidal effects of spraying with 25% suspension concentrate of niclosamide ethanolamine salt (25% SCN) and 50% wettable powder formulation of niclosamide ethanolamine salt (50% WPN), and dusting with 4% niclosamide ethanolamine salt dustable powder (4% DP) for controlling Oncomelania hupensis snails were investigated and compared in the fields, and the cost-effectiveness was analyzed. RESULTS: The corrected mortalities and the reduced rates of density of snails were 54.37%, 91.70%, 92.76%, 79.50%, and 59.55%, 95.93%, 97.63%, 94.15%, respectively, on 3, 7, 15, 30 d after spaying with 25% SCN, those on 3, 7, 15, 30 d after dusting with 4% DP were 59.10%, 91.83%, 95.56%, 93.34% and 65.03%, 94.93%, 97.61%, 97.28%, respectively; and those on 3, 7, 15, 30 d after spraying with 50% WPN were 76.29%, 91.68%, 93.12%, 81.59% and 81.24%, 97.02%, 97.84%, 95.27%, respectively. The cost of spraying with 25% SCN was 0.21 Yuan/m2, that of dusting with 4% DP was 0.39 Yuan/m2, and that of spraying with 50% WPN was 0.23 Yuan/m2 for snail control in the marshland. The cost of reduced one percentage of the corrected mortalities and the density of snails in controlling snails by 25% SCN, 4% DP and 50% WPN on 15 d were 22.68, 40.63, 25.17 Yuan and 21.54, 39.78, 23.95 Yuan, respectively. CONCLUSIONS: The three different formulations of niclosamide are reliable and effective for snail control in marshlands. There are some differences among the different molluscicides in start time, pharmacodynamic characteristics, spraying methods in the field, cost of snail control, and influencing factors. Therefore, we need reasonably select the suitable molluscicides according to the environmental characteristics and working condition.

Toxicological assessment of lambda-cyhalothrin and acetamiprid insecticides formulated mixture on hatchability rate, histological aspects, and protein electrophoretic pattern of Biomphalaria alexandrina (Ehrenberg, 1831) snails.

Several formulated mixtures of pesticides are widely used in modern agriculture. Nevertheless, the agriculture runoff causes a serious damage to the aquatic ecosystem. Therefore, the present study aims to use B. alexandrina snails as bioindicators for 30 g/l lambda-cyhalothrin and 17 g/l acetamiprid as a formulated mixture insecticide. Results showed that it has a molluscicidal activity against snails at LC50 7.9 mg/l. The hatchability percent of both treated 1-day-aged and/or 3-day-aged groups were less than that of the control group. The sublethal concentrations of the tested insecticide caused a remarkable abnormal necrosis in male and female gametogenic cells, besides a severe damage in both secretory and digestive cells. The results of SDS-PAGE protein profiles of treated snails showed that the least number of protein bands was noticed in snail groups that subjected to LC10 (6.6 mg/l) and LC25 (7.2 mg/l) concentrations when compared to control protein fractions.

Molluscicidal activity of Manilkara subsericea (Mart.) dubard on Biomphalaria glabrata (Say, 1818).

Schistosomiasis is promoted for species from Schistosoma genus affecting over 200 million people worldwide. Molluscicides are an efficient method to control this disease, being able to reduce intermediate host snail Biomphalaria glabrata number. In function of resistance cases using niclosamide, natural products are promisors to discover new drugs. Manilkara subsericea is endemic to Brazilian sandbanks of Rio de Janeiro State and wide ranges of biological activities. However, there is no studies evaluating its effects as molluscicidal agent. We tested crude extract from leaves of M. subsericea molluscicidal action, as well it ethyl-acetate fraction and isolated substances against B. glabrata. M. subsericea leaves crude extract and ethyl acetate fraction induced 80±4.13% and 86.66±4.59% mortality of adult snails at concentrations of 250ppm after 96h, and their LD50 values were 118.7±1.62 and 23.41±1.15ppm respectively. Isolated substances from M. subsericea were also considered active. Quercetin, myricetin and ursolic acid, at concentration of 100ppm (96h), were able to induce mortality levels of 100%, 80% and 53.33%, respectively. Our results suggest that M. subsericea can be considered promising as a molluscicide agent.

Review of Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of Euclea natalensis A.DC.

Euclea natalensis is traditionally used as herbal medicine for several human diseases and ailments in tropical Africa. This study reviews information on ethnomedicinal uses, botany, phytochemical constituents, pharmacology and toxicity of E. natalensis. Results of this study are based on literature search from several sources including electronic databases, books, book chapters, websites, theses and conference proceedings. This study showed that E. natalensis is used as traditional medicine in 57.1% of the countries where it is indigenous. Euclea natalensis has a high degree of consensus on abdominal pains, antidote for snake bites, diabetes, diarrhoea, malaria, roundworms, stomach problems, toothache, venereal diseases and wounds. Several ethnopharmacological studies have shown that crude extracts and chemical compounds from E. natalensis demonstrated many biological activities both in vitro and in vivo, which included antibacterial, antidiabetic, antifungal, antimycobacterial, antiviral, antioxidant, antiplasmodial, larvicidal, antischistosomal, molluscicidal, dentin permeability and hepatoprotective activities. Future studies should focus on the mechanism of biological activities of both crude extracts and chemical compounds from the species, as well as structure-function relationships of bioactive constituents of the species.

Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis.

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (¹H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis.

Modelling metaldehyde in catchments: a River Thames case-study.

The application of metaldehyde to agricultural catchment areas to control slugs and snails has caused severe problems for drinking water supply in recent years. In the River Thames catchment, metaldehyde has been detected at levels well above the EU and UK drinking water standards of 0.1 µg l-1 at many sites across the catchment between 2008 and 2015. Metaldehyde is applied in autumn and winter, leading to its increased concentrations in surface waters. It is shown that a process-based hydro-biogeochemical transport model (INCA-contaminants) can be used to simulate metaldehyde transport in catchments from areas of application to the aquatic environment. Simulations indicate that high concentrations in the river system are a direct consequence of excessive application rates. A simple application control strategy for metaldehyde in the Thames catchment based on model results is presented.

Active saponins from root of Pueraria peduncularis (Grah. ex Benth.) Benth. and their molluscicidal effects on Pomacea canaliculata.

BACKGROUND: Pueraria peduncularis (Grah. ex Benth.) Benth., which belongs to the Leguminosae family, exhibits resistance to many crop pests in agricultural production. Pomacea canaliculata is an important invasive snail in rice fields and causes severe yield losses. To evaluate the toxicity of P. peduncularis to P. canaliculata, in this study the molluscicidal activity of root extracts of P. peduncularis was tested against P. canaliculata; the active compounds were isolated, and the structures of these compounds were analysed using nuclear magnetic resonance (NMR) analysis and mass spectral analysis. RESULTS: Our results showed that the molluscicidal activity of the root crude extract differed between P. canaliculata with different shell diameters after treatment for 72 h. The median lethal concentration (LC50 ) was 5.511 mg L-1 against snails of 1.5 ± 0.2 cm diameter and 12.383 mg L-1 against snails of 2.5 ± 0.2 cm diameter. Furthermore, two active ingredients isolated from root methanol extracts were identified as pedunsaponin A and pedunsaponin C. Both pedunsaponin A and pedunsaponin C showed strong molluscicidal activities, with LC50 values of 3.893 and 4.252 mg L-1 , respectively, against snails with shell diameters of 1.5 ± 0.2 cm after treatment for 72 h. CONCLUSION: Pueraria peduncularis extracts exhibit high molluscicidal activity and have great potential value for exploring a molluscicide to control Pomacea canaliculata. © 2016 Society of Chemical Industry.

Discovery of molluscicidal and cercaricidal activities of 3-substituted quinazolinone derivatives by a scaffold hopping approach using a pseudo-ring based on the intramolecular hydrogen bond formation.

Discovery of novel topological agents against Oncomelania hupensis snails and cercariae remains a significant challenge in current Schistosomiasis control. A pseudo-ring formed from salicylanilide by an intramolecular hydrogen bond led to the discovery of 3-substituted quinazolinone derivatives which showed a potent molluscicidal and cercaricidal activities.

Low pressure UV/H2O2 treatment for the degradation of the pesticides metaldehyde, clopyralid and mecoprop - Kinetics and reaction product formation.

The degradation kinetics of three pesticides - metaldehyde, clopyralid and mecoprop - by ultraviolet photolysis and hydroxyl radical oxidation by low pressure ultraviolet hydrogen peroxide (LP-UV/H2O2) advanced oxidation was determined. Mecoprop was susceptible to both LP-UV photolysis and hydroxyl radical oxidation, and exhibited the fastest degradation kinetics, achieving 99.6% (2.4-log) degradation with a UV fluence of 800 mJ/cm(2) and 5 mg/L hydrogen peroxide. Metaldehyde was poorly degraded by LP-UV photolysis while 97.7% (1.6-log) degradation was achieved with LP-UV/H2O2 treatment at the maximum tested UV fluence of 1000 mJ/cm(2) and 15 mg/L hydrogen peroxide. Clopyralid was hardly susceptible to LP-UV photolysis and exhibited the lowest degradation by LP-UV/H2O2 among the three pesticides. The second-order reaction rate constants for the reactions between the pesticides and OH-radicals were calculated applying a kinetic model for LP-UV/H2O2 treatment to be 3.6 × 10(8), 2.0 × 10(8) and 1.1 × 10(9) M(-1) s(-1) for metaldehyde, clopyralid and mecoprop, respectively. The main LP-UV photolysis reaction product from mecoprop was 2-(4-hydroxy-2-methylphenoxy) propanoic acid, while photo-oxidation by LP-UV/H2O2 treatment formed several oxidation products. The photo-oxidation of clopyralid involved either hydroxylation or dechlorination of the ring, while metaldehyde underwent hydroxylation and produced acetic acid as a major end product. Based on the findings, degradation pathways for the three pesticides by LP-UV/H2O2 treatment were proposed.

[Molluscicidal effect of niclosamide ethanolamine salt powder - granula against Oncomelania hupensis].

OBJECTIVE: To evaluate the molluscicidal effect of niclosamide ethanolamine salt powder-granula (PG) against Oncomelania hupensis. METHODS: The molluscicidal experiment was carried out by the dusting method with niclosamide ethanolamine salt 4% PG. The experiments were respectively done in the laboratory and the tidal flats wetlands. At the same time, the niclosamide ethanolamine salt 4% dustable powder (DP) was as the control group. The single blind method was used for the quality control. The corrected mortality and the median lethal concentration (LC50) were compared between PG and DP in the molluscicidal experiment of the laboratory. The corrected mortality and the reduced rate of snails'density were compared between PG and DP in the tidal flats wetlands. RESULTS: The mortality rates of the snails were 96.67% and 100% respectively on 1 d after dusting 4.0 g/m2 of 4% PG and 2.0 g/m2 of 4% DP in the laboratory. The results showed that the mortality rates of the snails were higher with 4% DP than 4% PG in each dosage (t1 d = 3.60, P < 0.01). The LC50 (s) of 1d, 3 d, 7 d after dusting the molluscicide also showed that the molluscicidal effects of DP were better than PG. The corrected mortality rates were 91.71%, 92.91%, 90.57%, 85.33% and 71.09%, 90.11%, 90.13%, 85.26% on 3 d, 7 d, 15 d, 30 d after dusting with 4% PG and 4% DP, respectively, in the fields. Statistics showed that the mortality rates of snails were higher on 3 d, 7 d after dusting with PG than DP (χ23 d = 731.57, χ27 d = 25.90, P < 0.01), but there were no significant differences between PG and DP on 15d, 30d after dusting (χ215 d = 0.53, χ230 d = 0.01, P > 0.05). CONCLUSIONS: 4% PG has both the adsorption of powder and the penetrability of the granules. The molluscicidal effects of 4% PG and 4% DP are almost the same. However, the drift of the powder was still not effectively controlled. This problem need to be further studied.

[Oncomelania hupensis snail control effects of molluscicides with different formulations in field in marshland and lake regions].

OBJECTIVE: To observe the Oncomelania hupensis snail control effects of molluscicides with different formulations in the ditch with unstable water level in field of marshland and lake areas, so as to provide the evidence for formulating the prevention strategies. METHODS: A drainage channel with O. hupensis snails in Jiangling County, Jingzhou City were selected as the study field, then it was divided into 6 segments, except 1 segment was treated as the blank control group for observing the natural mortality rate of the snails, the other 5 segments were treated as observation groups, where 4% niclosamide ethanolamine salt powder, 5% niclosamide ethanolamine salt granule, 25% suspension concentrate of niclosamide ethanolamine salt, 26% suspension concentrate of metaldehyde and niclosamide ethanolamine salt, 50% niclosamide ethanolamine salt wettable powder were applied respectively. Before and after the mollusciciding, the snail surveys were carried out through the systematic sampling method, and the short- and long-term effects of snail control were observed, and the mortality rates of the snails on the slope above the water level and those below the water level were compared. RESULTS: When 7 d and 15 d after mullusciciding, the mortality rates of snails on the slope above the water level in each observation group were 79.52%-97.87% and 90.43%-96.30%, respectively, when compared with those before mollusciciding, all the differences were statistically significant (all P < 0.01). When 7 d after mullusciciding, the mortality rates of snails below the water level in each observation group were 17.11%-50.00%, which were all lower than those of the snails on the slope above the water level in the corresponding groups (all P ＜ 0.05); when 15 d after mullusciciding, the rates were 9.43%-95.24%, and those in 25% suspension concentrate of niclosamide ethanolamine salt, 26% suspension concentrate of metaldehyde and niclosamide ethanolamine salt, 50% niclosamide ethanolamine salt wettable powder groups were all lower than those of the snails on the slope above the water level in the corresponding groups (all P ＜ 0.01). Compared with the densities of living snails before mollusciciding, those 6 months after mollusciciding in each observation group decreased by 70.21%-78.98%. CONCLUSIONS: The molluscicides in the formulation of powders and granule are suitable for both the snail environment with or without water, while those in the formulation of suspension agents and wettable powders are suitable only for environments with water.

A Puna Collection of Senecio punae, Main Source of a Versatile Eremophilane-type Ketone.

Senecio punae Cabrera (Asteraceae-Senecioneae) is an endemic species from Puna semi-desert region of Argentina.The major compound, 4p,5p-eremophil- 7(11)9-dien-8-one, also known as dehydrofukinone (D), was isolated from the diethyl ether extract (E) of the plant. The phytochemical constituents from S. punae are presented here for the first time, as well as bioassays employing D, a molecule with versatility to carry out many different biological activities. E and D showed acute molluscicidal activity against the bilharzia vector snail Biomphalaria peregrina with LD50 values of 68.6 and 16.7 pg/mL, respectively. D exerted moderate and strong effects against promastigotes of Leishmania amazonensis and L. braziliensis, with IC5s values of 34.3?1.2 and 9.93+0.17 Ag/mL, respectively. Antibacterial effects were also found. Diethyl ether extract (E) and dehydrofukinone (D) were slightly active against Pseudomonas aeruginosa and Staphylococcus aureus at 50 and 25 tg/mL, respectively. However, D and E improved the effectiveness of oxacillin at 6 ig/mL against S. aureus growth and its biofilm, but did not affect beneficial lactobacilli strains. Synergistic effects were also measured between D (23 gg/mL) and ciprofloxacin (0.25 pg/mL) against two P. aeruginosa strains (FIC index = 0.38), as well as against two S. aureus strains (FIC indexes = 0.38 and 0.25). Finally, when 250 pg of either dehydrofukinone (D) or diethyl ether extract (E) were incorporated into the diet of the pest Oryzaephillus surinamensis, an alteration in the feeding behavior of the insect (Repellency indexes = +60 and +10, respectively) was observed.

Neocryptolepine: A Promising Indoloisoquinoline Alkaloid with Interesting Biological Activity. Evaluation of the Drug and its Most Relevant Analogs.

Plants are one of the most important resources for the discovery of new drugs. The potential of natural compounds as new drug leads is clearly illustrated by the discovery and development of many modern medicines. This is an encouraging factor that drives natural products research in the vegetable kingdom. Neocryptolepine is a tetracyclic nitrogen heterocycle isolated from the African climber Cryptolepis sanguinolenta, which is widely used in traditional African medicine in many countries of Central and West Africa. The natural product is one of the representative examples of the small family of indolo[2,3-b]quinoline alkaloids, being endowed of multiple biological activities, including DNA-binding and inhibition of the enzyme topoisomerase II. It is also cytotoxic, antibacterial, antifungal and molluscicidal, also displaying antiprotozoal activity, particularly as antitrypanosomal, antileishmanial, antischistosomal and antiplasmodial. Some of these activities have been related to the product's ability to bind to DNA and to inhibit topoisomerase II; however, the exact mechanisms behind all of the observed bioactivities have not been comprehensively clarified. Major research activities regarding neocryptolepine have been focused into two seemingly opposite fields, related to its cytotoxic and antimalarial properties. Optimization of the natural product as a cytotoxic agent implied improvements in its bioavailability and activity, while the need of non-cytotoxic compounds guided the design and optimization of antimalarial agents. Therefore, the aim of the present article is to systematically review the current knowledge about the diversity of the biological activities related to neocryptolepine, its analogs and derivatives.