Current Pharmaceutical Analysis - Volume 4, Issue 1, 2008

Understanding the interactions between proteins and ligands is crucial for the pharmaceutical and functional food industries. The experimental structures of these protein/ligand complexes are usually obtained, under highly expert control, by time-consuming techniques such as X-ray crystallography or NMR. These techniques are therefore not suitable for routinely screening the possible interaction between one receptor and thousands of ligands. To overcome this limitation, computational algorithms (i.e. docking algorithms) have been developed that use the individual structures of the receptor and ligand to predict the structure of their complex. The present review, then, summarizes: (a) the fundamentals of the algorithms of the most commontly used docking programmes (with particular emphasis on their strengths and limitations); (b) how the results from different docking algorithms compare (i.e. which software gives the best predictions); and (c) the future perspectives and challenges for docking techniques.

Folk medicine (FM) is practiced by people without access to conventional medical services; it usually involves the use of natural remedies such as herbs or vegetable substances. Before the use of pharmaceutical drugs, and surgical procedures, these healing methods were used, and are still in use today. It is estimated that twenty five percent of all therapeutic drugs trace their origins to plants, and almost two-thirds of the people of the world rely on their healing powers. One hundred years ago, health care in the U.S. was provided by a highly competitive medical sect, and quite infrequently, folk medicine practitioners were patronized. However, FM usage in the U.S. has increased drastically during the past decade. National surveys of adults (18 years of age or older) show that one in three adults use unconventional therapies or Complementary and Alternative Medicine (CAM) in the U.S. The rate of CAM usage is more than eighty percent among cancer patients. Vernonia amygdalina (VA) is well known for its medicinal importance. Fractionation of the VA extracts with solvents of varying polarities, by silica gels analyses, UV Spectrophotometer, HPLC, TLC and NMR techniques have yielded some biologically-active fractions.

Inorganic ions as well as organic acids or bases are frequently employed as counter-ions of ionizable drug substances. Therefore, analytical methods are required to confirm production of the correct salt form and to quantify the level of the counter-ion present in each batch of drug substances manufactured. Several options exist for determination of counter-ions in pharmaceutical salts and will be discussed in this review. Ion chromatography (IC) with conductivity detection is probably the most frequently employed method for ion determination. Other techniques such as capillary electrophoresis (CE) represent an alternative to IC for determination of counter-ions in pharmaceutical salts. Due to the lack of chromophores, detection of small ions in CE is typically performed using indirect UV detection. Hydrophilic interaction chromatography (HILIC) with evaporative light-scattering (ELSD) or refractive index detection can also be used for determination of non-UV absorbing ions. Each technique will be described and their advantages highlighted. Current and future trends in measuring counter-ions in pharmaceutical salts will also be discussed.

Pilocarpine (2(3H)-Furanone, -ethyldihydro-4-(1-methyl-1H-imidazol-5-yl)methyl]-) reacts with cobalt (II) in an acid medium and forms an electroactive complex with two sensitive reduction waves that are measurable using cyclic and differential pulse voltammetry on mercury-coated gold electrodes. We studied the electrochemical behaviors of this complex and its use for detecting pilocarpine in pharmaceuticals. We used carbon fiber with a surface deposit of mercury as a sensor in liquid chromatography-electrochemical detection (LCEC) to increase the sensitivity and selectivity of analytical methods for the determining trace concentrations of the cobalt (II)-pilocarpine complex.

A great amount of attention has recently been given to the water extracts of the basidiomycete Agaricus blazei, a kind of mushroom, to evaluate the applicability of their biological activity as an alternative medicine. Agaricus blazei is native to Brazil and was imported to Japan in 1965. Since Agaricus blazei was first cultured at Iwade Mycology Institute in Japan in 1975, its biological activity spectrum has been evaluated not only in in vivo, but also in in vitro experiments. Antitumor activity was first detected in Agaricus blazei water extracts in 1980. Since then, many groups have reported this antitumor activity, which results from polysaccharides such as β-D-glucans and their derivatives. In general, the antitumor activity appears to be mainly due to the activation of the immune system rather than to any direct effects of the water extracts on tumor cells. This idea is supported by the fact that macrophages derived from rat bone marrow were activated and cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-8, and nitric oxide (NO) were secreted, in response to these water extracts in in vitro experiments. Furthermore, oral administration of Agaricus blazei water extracts to mice induced the activation of macrophages and T cells in vivo. Anti-genotoxic, anti-mutagenic and anticlastogenic effects were also detected in Agaricus blazei water extracts. As well, anti-viral activity of Agaricus blazei hypha water extracts was observed on the cytopathic effects induced by Western Equine Encephalitis (WEE) virus in vitro. Thus, based on both in vivo and in vitro experiments, Agaricus blazei water extracts appear to have great potential for development as alternative medicines.