Natural products pharmaceutical decline

The past decades witnessed a major decrease in the number of newly discovered compounds. In an almost 40-year period (1962-2000), no new class of antibiotic was introduced to the market (nalidixic acid in 1962, the oxazolidinone antibiotic linezolid in 2000) [44, 45]. The major reason for the decrease in the number of newly discovered compounds might be a decline in screening efforts [37]. Ironically, some of the leading pharmaceutical companies are currently cutting back their antiinfective programs, especially for natural products [46]. They rather focus their activities on the semisynthetic modification of existing antibiotics to produce second- and third-generation antibiotics with improved properties. 

Although combinatorial chemistry has been employed in the pharmaceutical industry over the last 2 decades to satisfy the need for very large numbers of compounds demanded in high-throughput screens (HTS), the results have not been as promising as expected, and the number of new chemical entities introduced annually as produced by this method has actually declined [3, 17]. A combination of natural products and combinatorial chemistry has been initiated in recent years. In this case the latter serves as a technique to optimize the structure of existing active natural compounds to new agents [17-20]. 

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