Sources of Active Principles

The huge reseivoir of as-yet untapped molecular structures is evidenced in the microbial world by the assessment of the microbial diversity. 

Natural products are an indispensable source for novel structures and chemical diversity for drag discovery. Aquatic sources and plant sources are an underutilized source of active principles or lead compounds. 

Extremophiles are a source of evolution-hardened enzymes and principles, such as thermostable enzymes (Taq polymerase for PCR) and cold-adapted enzymes with applications in the detergent and food industries, fine chemicals production, bioremediation as well as broader applicable mechanisms for then- high catalytic efficiency based on stractural X-ray studies. 

Commercial evidence also supports the case for natural products. Of the 20 best-selling non-protein drags in 1999, nine were either derived from or developed as the result of leads generated by natural products (e.g., simvastatin, lovastatin, ciprofloxacin, clarithromycin and cyclosprin) with combined annual sales of greater than US 16 billion. Newer developments based on natural products include the antimalarial drag artemisinin, and the anticancer agents taxol, docetaxel and camptothecin. In addition to the historical success in dixig discoveiy, natural products are likely to continue to be sources of new commercially viable 

Studies of physiological responses at the protein level lead to targets for therapies. For example, heat-shock and stress proteins, synthesized as a response to external or immunologic stress, provide targets for immunotherapeutic interventions.  

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The drag discovery process is the fundamental source of active principles, i.e. compounds which interact as agonists or antagonists, functionally or stractnrally, with constitnents of living organisms. 

Nature was the first source of active principles, albeit in ciude, dilute, mixed and sometimes toxic forms, an early example being quinine (present in Cinchona baik). 

Most active principles and pharmaceutical forms are processed in the presence of organic solvents or reagents. The current regulations on products generally restrict to a few p.p.m. the amount of residual solvent. This very low concentration level could favour the CO2 utilization when non-polar compounds have to be eliminated. On the other hand, the elimination of residual solvents from tablets, films or other pharmaceutical preparations in which organic solvent are involved has been addressed [15]. Another application is related to the removal of residues from medical materials such as monomers, additives or polymerization residues from polymers or elastomers. Purification of active principles includes elimination of other undesired molecules pesticides from some vegetal extracts, and antibacterials suspected of toxic co-extracts from natural sources. 

This mathematical process can cope with any type of detector, any type of source. In principle, it can generate efficiency curves relevant to anything from a point source measured on-axis to an infinite plane source of activity measured at an angle - all without radioactive sources. There are, however, drawbacks. Unless all samples are identical in shape, density and composition, a separate efficiency curve would need to be calculated for each sample. Depending upon the complexity of the model and the speed of the computer. 

To outline how this has come about, in other words, to examine the role of curare in the development of modern muscle relaxants, is the aim of the present review. But it is also concerned with the plants that are the sources of activity and with the substances that are their active principles. Certain aspects of the pharmacology, including the mode of action, of these compounds and the development of the muscle relaxants derived from them are also outlined. 

Where to chemical syntiiesis is not viaUe then the active imnciple must be obtained either completely or partially from a natural source. Often, however, active principles are present only in minute amounts in material fmn the source plant. The classical example of this situation refers to the anti-leukaemic dimeric alkaloids vincristine and vinblastine from Catharanthus roseus. These compounds may be obtained from the leaves of periwinkle plants grown in the field, but the yield of active principle is less than 0.001% (w/w) making these amongst die most expensive of drugs. Similariy, die content of artemisinin in A. annua has been shown to be rather low and variaUe widiin die range 0.003 -0.21% w/w (8). 

Alpha counting is done with an internal proportional counter or a scintiUation counter. Beta counting is carried out with an internal or external proportional gas-flow chamber or an end-window Geiger-MueUer tube. The operating principles and descriptions of various counting instmments are available, as are techniques for determining various radioelements in aqueous solution (20,44). A laboratory manual of radiochemical procedures has been compiled for analysis of specific radionucHdes in drinking water (45). Detector efficiency should be deterrnined with commercially available sources of known activity. 

The sources of error indicated above were avoided in a series of experiments carried out by Donnan and Barker, which in principle resemble those made by Lewis, so that only a brief reference to them is necessary. The dissolved substance was nonylic acid, and a drop method. The results could be reproduced with very great accuracy, i.e., to a fraction of one drop in 300—500 drops. Adsorption was produced at a surface air-liquid, air being passed through the solution in bubbles of known size and number, so that the total active surface could be calculated. The bubbles, on reaching the surface, burst, hence the excess of solute carried by them remained in the surface very effective precautions were used to prevent diffusion backwards from this portion into... 

An important number of these substances have an industrial origin. Some of them, like the pesticides, arrive intentionally in the environment and their use and release should be theoretically controlled. However, many of them have not been purposely produced as bioactive substances but more as components or additives of certain materials. Their significant growth in the chemical industry has not only been produced as a consequence of the discovery of new active principles in the pharmaceutical or pesticide area, but also because of the expansion of new technologies (electronics, containers, textiles, plastics, resins, foams, etc.), that require the development of new materials and substances with particular features. Most of these substances enter or are discharged to water and air sources without regulated controls. Wastewater treatment plants (WWTPs) are often not yet adapted to completely remove them, and therefore these new compounds can be found to some extent in wastewater effluents as well as in soil and sludge. 

Sulfur has four unique characteristics related to its occurrence and chemistry in soil. As sulfate, it is one of the principle counterions that keep the soil electrically neutral. Soil receives constant additions of sulfur through volcanic activity around the world and industrial pollution, usually in the form of acid rain. This means that soils usually have sufficient sulfur for plant growth. Lastly, plants can take and use sulfur dioxide from the air as a source of sulfur for growth [22,38],... 

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