Lead compounds drug discovery

AMC is still a popular dye today. According to our experience, the IC50 values determined for protease inhibitors in AMC-based protease assays may be biased and misinterpreted due to the interference of label and compound autofluorescence characteristics (Figure 2.3). In the worst case, this can lead a drug discovery program in a wrong direction with respect to prioritization of compound classes. At the excitation and emission wavelengths of 350 and 500 nm, respectively, used for AMC, many compounds also display fluorescence characteristics. 

No other single phylum has been more productive than that of the marine Porifera in producing leads for drug discovery and molecular tools. The remarkable activity of the cytotoxic compounds 1-19 (Scheme 6.1 Parts 1 and 2) have led to the development of marine natural products and their congeners as leads in numerous anticancer clinical trials. The actin inhibitors 20-26 (Scheme 6.1 Part 3) have led to the use of sponge-derived agents as probes in the study of cellular processes. In addition, a number of unique structures such as 27-31 (Scheme 6.1 Part 4) have potential as leads in the treatment of other persistent maladies such as asthma, pain and malaria. 

A major challenge in any drug discovery program is achieving reasonable bioavailability upon oral administration therefore, any information that highlights potential problems with cell permeability and absorption is valuable when reviewing structural families as leads for drug discovery. Lipinski et al. [3] have reviewed 2245 compounds selected from the United States Adopted... 

The screening of chemical libraries is one of the major sources for new leads in drug discovery. The large size of chemistry space compared with the library sizes that are feasible to screen requires careful selection of the compounds for the screening library to maximize screening success. 

In this chapter, the structures, the source, and bioactivity of selected classes of typical marine alkaloids are described. The emphasis is on compounds that have emerged as novel leads, such as lamellarins (pyrroles), cephalostatins/ritterazines (pyrazines) and ecteinascidins (isoquinolines), and manzamines (P-carbolines) to give relevance to the role of marine alkaloids as an important source of leads for drug discovery. 

The use of semi-synthetic derivatives as drugs developed from plant natural product lead compoimds began at the end of the nineteenth century and may be exemplified by drugs like aspirin (acetyl salicylic acid). From then on, the potential of plant-derived compounds as leads in drug discovery has been realized on numerous occasions [8], A survey released recently revealed that over 40% of the new small-molecular single chemical entity drugs introduced to the market from 1981 to 2006 are natural product derivatives, with 28% of them being chemical semi-synthetic modifications... 

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