From Introduction: That bilharziasis an important public health, social and economic problem in the tropical and subtropical countries of the world is well appreciated. (WHO, 1965) Bilharsiasis is the disease caused by parasitic worms of the genus Schistosoma having certain fresh water snails as the intermediate host. In South Africa the more important snails are Bulinus africanus and B. globosus, the secondary hosts of Schistosom haematobium. (WHO, 1965) One method of controling the disease is to reduce the numbers of the intermediate host snails to such a low level that transmission cannot occur (WHO, 1965 and Macdonald, 1965) This has led to a strong interest in those substances that kill snails. The first recorded use of a molluscicide, copper sulphate, was during the first world War in Egypt. (De Villiers, 1965) More recently, the more or less random testing of large numbers of compounds led to the discovery of a large number of molluscicides. These were the heavy metal compounds such as the salts of mercury and arsenic, the substituted phenols such as pentachlorophenol (PCP) and the 2-substituted 4:6-dinitrophenols. (De Villiers, 1965) These compounds are good molluscicides but suffer from a number of disadvantages. The use of copper compounds in hard waters is impractical as the copper precipitates out as the less effective carbonate. The heavy metal salts are expensive and biocidal thus making the treated water unsuitable for human or agricultural use. The phenolic compounds are unpleasant and dangerous to handle and the hydrolysis of PCP is catalysed by sunlight in clear waters. High concentrations of these compounds are required, thus increasing transport and handling costs, particularly in inaccessible areas.

The use of plants with molluscicidal properties IS a simple, inexpensive and appropriate technology for focal control of the snail vector. Isolation and identification of the active constituents is essential for the study of their toxicities and stabilities under field conditions, for dosage purposes, for structureactivity investigations and for effects on snail metabolism or physiology. It is in this context, that an investigation into molluscicides and other compounds from indigenous plants has been carried out. From Apodytesdimidiata subsp. dimidiata, betulinic acid (53) genipin (49) and lO-acetyl genipin (58) have been isolated and the last two have proved to possess molluscicidal activity. Furthermore, 4-ethylcatechol (60) isolated from Gardenia thunbergia is one of the most powerful naturally-occurring molluscicides. / Thesis (M.Sc.)-University of Natal, Pietermatizburg, 1996.

No description available.

The aim of the project was to synthesize warburganal, a natural product isolated from the Warburgia plants native to Venda, known as a potent molluscicide, in a new, cheaper and more efficient way to be used in the ongoing war against bilharzia. A synthetic pathway beginning with geraniol as the starting material was planned to afford a 7-step route. The first step involved the substitution of a bromine group for a hydroxyl group. Geranyl bromide underwent an alkylation step with the dianion of methyl acetoacetate to afford methyl 3-oxo-7, II-dimethyldodeca-6E, IO-dienoate. The . next Lewis acid-catalyzed step involved formation of the bicyclic decalin ring system, methyl (IR* ,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate. The next step was to add a hydroxyl group alpha to the ester, the a-OH being vitally important to the biological activity of warburganal. This step proved to be unsuccessful with the methodology used. A change in tactics was obviously required and initially protection of the ketone as an acetal was attempted. Instead of the expected acetal product, an epimer of the decalin structure above, namely, methyl (IS*,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate was isolated. This epimer seems to form under acidic as well as basic conditions and was also isolated from an a-hydroxylation reaction that employed KH and MoOPH. Most of the steps were attempted on model compounds to enable the conditions to be optimized prior to attempting the reaction on the warburganal precursor. It was soon discovered that for reasons as yet unknown, the reactions that worked on the model compounds did not always work on the warburganal precursors, although the model compounds possessed functional groups that best simulated those possessed by warburganal. The progress reported towards the synthesis of warburganal highlights the many difficulties encountered when introducing the requisite functional groups on to the decalin ring skeleton to afford warburganal i. e. the a-hydroxyl and p-aldehyde moieties and the a,p-unsaturated aldehyde. Although the planned synthetic pathway was not entirely successful, the pitfalls encountered are discussed and potential solutions are presented. A number of interesting and unexpected compounds were isolated en route and ideas are discussed that may well culminate in an efficient synthesis of warburganal. / Thesis (Chemistry)-University of Natal, Pietermaritzburg, 1998.

Despite more than half a century of international research on schistosomiasis control, this disease remains a public health concern in many Third World countries. Four to five percent of the world's population is estimated to be infected. In South Africa, bilharzia is prevalent in rural communities which lack piped water and adequate sanitation. Transport and treatment costs limit access to Western medication. In the last decade, plant molluscicides have received considerable attention in the ongoing search for cheaper alternatives to chemotherapy and synthetic molluscicides. Plant molluscicides may be locally harvested, extracted and applied for the control of the snail host. This approach is based on a philosophy of self-reliance and self-determination. However, such involvement presupposes recognition of the infection as a real problem. Before selecting and evaluating plants for molluscicidal activity, it was first necessary to establish the status of schistosomiasis in rural communities, and the willingness of community members to become involved in control efforts. Field surveys showed that rural South African communities do not share the indifference of the past health-care system towards schistosomiasis in this country. Concern for the disease was matched by a prevalence of 75.14% for S. haematobium in the study area. The potential of the South African flora to provide suitable molluscicidal candidates has never been systematically assessed . As random screening is costly and is historically of limited success, a need has existed for the development of an objective selection procedure . A simple scoring system was devised, based on the criteria for "good" plant molluscicides as defined by the World Health Organization (WHO). Three plant species were subsequently selected for further intensive evaluation: Warburgia salutaris, Gardenia thunbergia and Apodytes dimidiata. Initially, the activity of crude aqueous suspensions of all three candidates was investigated, since this application form is the most practical for use in a rural situation. Further, the stability of extracts under changing physical and chemical conditions was assessed, as were t he effects of molluscicides on a wide range of to the toxicity of aqueous suspensions, cultivation potential, medicinal value, stability, and toxicity to non-target organisms. Studies on the mode of action of the three plant extracts revealed that death occurred via distinct physiological pathways; this despite the similarities in clinical symptoms. Such is the complexity of snail physiology that until more intensive neurological investigations are undertaken, the mechanisms of molluscicidal action can only be inferred. Chemical compounds responsible for activity were identified from Apodytes dimidiata; genipin, a monoterpene, was one such active constituent. Although not previously recorded as molluscicidal, earlier workers have isolated genipin from Genipa americana and Gardenia jasminoides. Notably, this compound has not yet been isolated from Gardenia thunbergia. Further activity in A. dimidiata extracts appeared to be the result of a synergistic effect, potentially involving (S)(-) ethyllactate. Research on mammalian toxicity, and registration procedures for plant molluscicides in South Africa should be prioritized for further investigation, before pilot field trials are initiated. Almost thirty years have passed since the first reports on the activity of Phyto!acca dodecandra. Although more than 1000 plant species have since been tested world-wide, it appears that no plant molluscicide has ever been endorsed by the WHO. More concerted efforts are necessary to ensure that appropriate molluscicidal technologies are provided to infected communities. / Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1994.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Includes bibliographical references (leaves 152-169).

Schistosomiasis is an important public health issue for rural communities located near,or around slow moving water bodies in the tropical and subtropical areas. Successful control of the disease involves multifaceted approaches, which include snail control, environmental sanitation, health education and chemotherapy. Although snail control might be an effective method of controlling schistosomiasis, there has been a general lack of control initiatives, largely due to the cost of available molluscicides. Plants offer a wide array of compounds which, on extraction, may show molluscicidal activity. If molluscicidal compounds that occur in indigenous plants can be extracted using local labour and simple technology, then there should be culturally acceptable and inexpensive molluscicides. The aim of this study was, therefore, to screen some Zulu medicinal plants for molluscicidal activity. We have also attempted to isolate the active chemical compounds from such plants. Aqueous and methanolic crude extracts of ten (10) Zulu medicinal plants, used for different medicinal and domestic purposes, were screened for molluscicidal activity on Biomphalaria pfeifferi and Bulinus africanas snails reared in the laboratory during the time of bioassay. Bayluscide® (niclosamide) was used as a positive control for comparison, while de-chlorinated tap water was used as the negative control. Six of the plants were not active against the snails. Extracts from four of the plants demonstrated weak to moderate molluscicidal activities. These plants are: (i) Sclerocarya birrea stembark, (ii) Psidium guajava (hybrid) leaves, (iii) Leonotis leonurus aerial parts and (iv) Ekerbegia capensis stem-bark. The LC50 values of the plant extracts were 78 ppm, 100 ppm, 398 ppm and 600 ppm respectively. Of the 4 plants that showed molluscicidal activity, S. birrea aqueous and methanol extracts were the most active against the snails, with LC50 values of 82 ppm and 78 ppm respectively. For the other plant extracts, only the methanolic extracts showed activity. Brine shrimp toxicity assay was performed with all the active extracts. Psidium guajava showed 10% survival of the shrimps at 1000 ppm, whereas no survival was observed for the other plant extracts at this concentration (1000 ppm). The results obtained in this study indicate that further studies have to be conducted, especially with S. birrea extracts, whose both aqueous and methanolic extracts showed significant activity against the snails. / Thesis (M.Med.Sc.)-University of Durban-Westville, 2002.

The studies described herein focused on the use of intermittent halogenation to control biofouling of water intake systems by the zebra mussel, Dreissena polymorpha, the comparative response of zebra mussels and the Asian clam, Corbicula fluminea, to a surfactant -based chemical control agent, the nontarget impact associated with the control agent, and the use of the Asian clam as a biomonitor of the control agent. Effects of intermittent (2-4 hr/day) treatments with chlorine or bromine at levels of 0.5 and 1.0 mg/L (total residual oxidant) upon settling of zebra mussel veligers were examined in studies conducted in a field laboratory on western Lake Erie. Veliger densities in the water column at the field site peaked at 530/L, while mussel densities on settling monitors reached 147,083/m² over the course of the study period. Zebra mussel settling in test systems treated with the halogens was reduced by as much as 91 % in comparison with controls, although mussel densities of up to 6,044/m² still occurred. Treated mussels which remained settled had growth rates similar to controls, and reached 2-4 mm length over 30 days. The intermittent halogen treatments had no significant impact on either adult zebra mussels or Asian clams. The studies indicate that while the treatment regimes may reduce zebra mussel densities within intake systems, the threat of eventual fouling due to cumulative settling remains. / Ph. D.

The brazilian is biodiversity considered one of higher of the world, is a bit know and explored as the source of drugs medicines. In search of new bioactive molecules the etanolic extract of stem of Serjania lethalis St. Hil was studied in for the molluscicide, miracicide and shistossomicida activity. The specie S. lethalis was collected in Brasilia and a voucher is deposited in the Herbarium of Federal University of Brasilia under the number JEP 3698 UB. After dried end reduced to powder the stem of S. lethalis was extracted in Soxhlet apparatus with ethanol 95%. The crude ethanol extract of stem was extracted, at low temperature, with acetone. The soluble fraction in acetona was purified through filtration in active charcol and permeation in sephadex gel LH 20 and additional preparative chromatographic plate for the obtention of saponin codified as SLS. An alternative method of separation involving the use of synthetic membranes that provide dialysis was used for hidrometanolic and ethyl acetate fractions obtained from the partition of the liquid-liquid crude ethanol extract (stem). Due to the antibacterial activity observed after dialysis follow up purification was made, using chromatography techniques on column with deacttived sílica and subsequent purification in Sephadex LH 20 column to obtain the SLD substance. The butanolic fraction obtained from liquid-liquid partition was active against Biomphalaria glabrata with CL90 10,62 μgmL-1 in 24 hours. The fraction soluble in acetone showed excellent inhibition halo against Pseudomonas aeruginosa. The chemical structures of pure substances SLS, 3-O-[β-Ogalactopyranosyl (1 4)-α ramnopiranosil (1 2) α-ramnopiranosil and SLD, O-β Dfructofuranosil-( 2 4)-D - glucose were proposed based on data from unidimensional Nuclear Magnetic Resonance (NMR) (NMR 1H, NMR 13C, DEPT 135) and two-dimensional (COSY, HSQC and HMBC). The in vitro test showed that the substance codified as SLS was active against S. mansoni. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A biodiversidade brasileira considerada uma das maiores do mundo ainda é pouco conhecida e muito pouco explorada quanto ao uso como fonte de medicamentos. Na busca de novas moléculas bioativas o extrato etanólico do caule da Serjania lethalis St. Hil foi estudado na busca do princípio ativo responsável pela atividade moluscicida, miracicida e esquistossomicida. A espécie S. lethalis foi coletada em Brasília e uma exsicata encontra-se depositada no herbário da Universidade Federal de Brasília sob o número JEP 3698 UB. Após seco e reduzido a pó o caule de S. lethalis foi extraído com etanol em um aparelho do tipo Soxhlet. O extrato etanólico bruto do caule foi extraído, a frio, com acetona. A fração acetônica (solúvel) foi purificada por meio de partição em carvão ativo e permeação em gel sephadex LH 20 e adicional cromatografia em placa de camada preparativa para a obtenção da saponina codificada como SLS. Um método de separação alternativo, envolvendo o uso de membranas sintéticas que proporcionam diálise foi utilizado para as frações hidrometanólica e em acetato de etila provenientes da partição líquido-líquido do extrato etanólico bruto (caule), devido à atividade antibacteriana observada. Após a diálise a purificação foi realizada, com utilização de técnicas cromatográficas como cromatografia em coluna de sílica desativada e posterior purificação em coluna de Sephadex para chegar a substância SLD. A fração em butanol obtida da partição líquido-líquido foi ativa frente ao molusco Biomphalaria glabrata com CL90 10,62 mgmL-1 em 24 horas. A fração solúvel em acetona apresentou excelente halo de inibição frente a Pseudomona aeruginosa. Ao final as estruturas químicas das substâncias puras 3-O- [β- O- galactopiranosil (1 4) α- ramnopiranosil (1 2) α- ramnopiranosil (SLS) e O-β-D-fructofuranosil-(2 4)-D-glucose (SLD) foram propostas com base em dados de Ressonância Magnética Nuclear (RMN) unidimensional (RMN H1, RMN C13, DEPT 135º) e bidimensional (COSY, HSQC e HMBC). O teste in vitro demonstrou que a substância codificada como SLS foi ativa frente ao S. mansoni.