Developing Potent Anti-Plasmodium Molecules.
A Complex Disease - Malaria can be said to be the most prevalent and the most pernicious. Caused by a Protozoan parasite, Plasmodium species (four species), the disease causes fatality in nearly 2.7 to 3 million human individuals most of whom are children below 5 years (Spelman, 2009 p.1). Simply the disease causes high fever due to medical immunity related disturbances in the body. The only reliable method available for confirmed diagnosis of this disease is microscopic observations of parasite cells in the blood. The parasite gets into the blood due to bite of a mosquito vector, Anopheles sps. Thus the disease is complex because it lives both in mosquitoes and men showing many intermediary distinct stages in its life cycle.
Control of this disease has become more demanding because the previous successfully used methods for control have become unsuccessful because both the parasite and the vectors have developed resistances to their respective controlling chemicals such as chloroquinine and DDT. The infected mosquito vector populations of Plasmodium can neither be disinfected nor killed because of their all-pervasive nature and universatility. The disease is asymptomatic. Even the existing diagnostic method can give misleading andor erroneous negativespositives.
Inadequate Treatment Chloroquinine was the historical and safe method for treatment but Plasmodium has developed resistance to this drug. Post-quinine based drugs, Artemesinin, an alkaloid from Artemisia spp., singly initially and then in combination with other drugs were the used. But unfortunately the parasite has acquired immunity to even these.
Since then aggressive researches rapidly adopting the latest molecular biological technologies on different aspects of the pathogenesis biology of the parasite both in the vector and the host have been making just optimistic claims about the potentials of the drugs still to be developed on the controls. The different parasite stages in liver and blood of the host, and mouth-saliva and gut of mosquitoes only confound the directions of treatment complexity. Recent interest in the development of blocking of transmission of the parasite from hosts to vectors is only clearing the known and unknown gaps in the knowledge. Transgenic approaches have been actively investigated in spite of many environmental, ethical and regulatory hurdles. Yet the optimism remains
Just by developing science and technologies for transmission prevention between a vector to host and vice versa is unlikely to contribute to sustained control of malarial disease. Based on the confidence in the past success of quinine-based and artimesinin (a sesquiterpene lactone) - based, both of which are plant derived molecules, there has been a silent but steady interest in exploration of other potential plants as sources of other molecules from the rich plant bio-diversity. Over 1,277 plant species from 160 families listed that have been used to treat malaria (Willcox 2004, cited by Spelman, 2009). For exploring anti-plasmodium herbal parts and extracts procedures used may be as follows.
Plant Parts and Extracts Different promising parts of different plants would be used on the basis of existing use literature in different folk and ethic medicine (Bero et al., 2009 p 1). Based on their review of literature it becomes clear that plant species of Asteraceae, Caesalipiniaceae and Leguminoasae contain a wide variety of bio-molecules that have been reported to be showing high (IC50 d 2 mM) in vitro activity against various strains of Plasmodium falciparum ((Bero et al., p. 1428). They have highlighted different potential compounds for development towards antiplasmodial drugs. This paper should give good lead in this context. Plants and their parts would also be based on availability of potential anti-plasmodial molecules available. In the traditional medicine systems most of the time water extracts. But in this significant paper there are very valuable antiplasmodial compounds which are lipophilic and therefore insoluble aqueous solutions.
Recently the need concerted efforts in such directions have provided workable techniques for bioassay-based fractionation and separation of the crude extracts. For instance, Cimanga et al (2006) reported that among ethanol, dichloroethane and petroleum ether the latter solvent yielded potent molecules for above 60 reduction in parasitemia in vivo rodent tests to Plasmodium berghei.
Urgency of a safe cheap and potent antiplasmodial molecule demands a rapid development of an alternative antimalarial drug. Recently a technique called the high throughput screening has been developed for testing accurately effective molecules in short time in relation to many other major and serious human diseases.
Research Proposal This research proposal on screening potential antiplasmodial molecules from the richly documented plant sources ( Bilia et al, 2005 Canoto et al., 2003 Kaur., 2009 Mambu et al., 2008 Saxena et al., 2003 and Schwikkard and van Heerden, 2002).
Efforts will also be made on the mechanism of action of some most effective molecules on the malarial parasite based on current techniques and literature.
Objectives
To screen different plant species known in the folklore and ethnic medicine for malaria treatment.
Some selected solvents known for extraction of specific anti-malarial molecules (example different kinds of alkaloids) would be used for extracting different parts sequentially and sequentially. Standardize the best and easiest combinations for bio-assay tests on in vitro and in vivo anti-plasmodial activity
The effective solvent extracted antiplasmodial molecules would be tested on a wide range of mainly chloroquine resistant Plasmodium falciparum strains as well as those of chloroquinine sensitive categories.
In many instances such promising effective molecules would also be tested for other major animal and human diseases such as cancers and HIV, Flu and so on because some of them have shown good results.
Approaches From the literature survey it becomes clear that the major effort has been to rely on various popular folk and ethnic medicinal plants used in different geographic boundaries. Incidentally it is mostly in those areas that malarial disease is most prevalent and serious. Several efforts on identification of their respective potential anti-plasmodial molecules and their effective anti-plasmodial concentrations have been done on single molecules in nearly all the reports.
In this work the efforts will be towards combining these molecules at their optimum tested concentrations in different permutations and combinations for faster better efficacy at cheap costs without having to resort to further chemical modifications for better efficacies.
Control of this disease has become more demanding because the previous successfully used methods for control have become unsuccessful because both the parasite and the vectors have developed resistances to their respective controlling chemicals such as chloroquinine and DDT. The infected mosquito vector populations of Plasmodium can neither be disinfected nor killed because of their all-pervasive nature and universatility. The disease is asymptomatic. Even the existing diagnostic method can give misleading andor erroneous negativespositives.
Inadequate Treatment Chloroquinine was the historical and safe method for treatment but Plasmodium has developed resistance to this drug. Post-quinine based drugs, Artemesinin, an alkaloid from Artemisia spp., singly initially and then in combination with other drugs were the used. But unfortunately the parasite has acquired immunity to even these.
Since then aggressive researches rapidly adopting the latest molecular biological technologies on different aspects of the pathogenesis biology of the parasite both in the vector and the host have been making just optimistic claims about the potentials of the drugs still to be developed on the controls. The different parasite stages in liver and blood of the host, and mouth-saliva and gut of mosquitoes only confound the directions of treatment complexity. Recent interest in the development of blocking of transmission of the parasite from hosts to vectors is only clearing the known and unknown gaps in the knowledge. Transgenic approaches have been actively investigated in spite of many environmental, ethical and regulatory hurdles. Yet the optimism remains
Just by developing science and technologies for transmission prevention between a vector to host and vice versa is unlikely to contribute to sustained control of malarial disease. Based on the confidence in the past success of quinine-based and artimesinin (a sesquiterpene lactone) - based, both of which are plant derived molecules, there has been a silent but steady interest in exploration of other potential plants as sources of other molecules from the rich plant bio-diversity. Over 1,277 plant species from 160 families listed that have been used to treat malaria (Willcox 2004, cited by Spelman, 2009). For exploring anti-plasmodium herbal parts and extracts procedures used may be as follows.
Plant Parts and Extracts Different promising parts of different plants would be used on the basis of existing use literature in different folk and ethic medicine (Bero et al., 2009 p 1). Based on their review of literature it becomes clear that plant species of Asteraceae, Caesalipiniaceae and Leguminoasae contain a wide variety of bio-molecules that have been reported to be showing high (IC50 d 2 mM) in vitro activity against various strains of Plasmodium falciparum ((Bero et al., p. 1428). They have highlighted different potential compounds for development towards antiplasmodial drugs. This paper should give good lead in this context. Plants and their parts would also be based on availability of potential anti-plasmodial molecules available. In the traditional medicine systems most of the time water extracts. But in this significant paper there are very valuable antiplasmodial compounds which are lipophilic and therefore insoluble aqueous solutions.
Recently the need concerted efforts in such directions have provided workable techniques for bioassay-based fractionation and separation of the crude extracts. For instance, Cimanga et al (2006) reported that among ethanol, dichloroethane and petroleum ether the latter solvent yielded potent molecules for above 60 reduction in parasitemia in vivo rodent tests to Plasmodium berghei.
Urgency of a safe cheap and potent antiplasmodial molecule demands a rapid development of an alternative antimalarial drug. Recently a technique called the high throughput screening has been developed for testing accurately effective molecules in short time in relation to many other major and serious human diseases.
Research Proposal This research proposal on screening potential antiplasmodial molecules from the richly documented plant sources ( Bilia et al, 2005 Canoto et al., 2003 Kaur., 2009 Mambu et al., 2008 Saxena et al., 2003 and Schwikkard and van Heerden, 2002).
Efforts will also be made on the mechanism of action of some most effective molecules on the malarial parasite based on current techniques and literature.
Objectives
To screen different plant species known in the folklore and ethnic medicine for malaria treatment.
Some selected solvents known for extraction of specific anti-malarial molecules (example different kinds of alkaloids) would be used for extracting different parts sequentially and sequentially. Standardize the best and easiest combinations for bio-assay tests on in vitro and in vivo anti-plasmodial activity
The effective solvent extracted antiplasmodial molecules would be tested on a wide range of mainly chloroquine resistant Plasmodium falciparum strains as well as those of chloroquinine sensitive categories.
In many instances such promising effective molecules would also be tested for other major animal and human diseases such as cancers and HIV, Flu and so on because some of them have shown good results.
Approaches From the literature survey it becomes clear that the major effort has been to rely on various popular folk and ethnic medicinal plants used in different geographic boundaries. Incidentally it is mostly in those areas that malarial disease is most prevalent and serious. Several efforts on identification of their respective potential anti-plasmodial molecules and their effective anti-plasmodial concentrations have been done on single molecules in nearly all the reports.
In this work the efforts will be towards combining these molecules at their optimum tested concentrations in different permutations and combinations for faster better efficacy at cheap costs without having to resort to further chemical modifications for better efficacies.
Categories:
0 коммент.:
Отправить комментарий