Microbial natural product derivatives

The most remarkable property of these derivatives of microbial natural products is the wide margin of safety accorded to treated mammals - the reason being that the drug does not readily cross the blood-brain barrier to any extent (18). Fortunately in mammals, GABA mediated nerves only occur in the central nervous system. 

Although use of marine microbial sources for the discovery of natural products is a somewhat recent phenomenon, marine natural products from higher species have contributed tremendously to the discovery of novel architecturally complex compounds as anticancer agent leads with one, Ecteinascidin-743, now approved in the European Union for treatment of sarcoma. The discovery of natural products derived from marine sources exploded in the 1970s not only because of increased... 

Contraction in the number of EPA-allowed biocides has heightened efforts to develop naturally derived preservatives and microorganisms capable of countering microbial degradation. Neem oil A. dirachta indica seed extract) has been featured as an exceptional natural candidate for the preservation of cosmetic products. Naturally derived chemicals with antimicrobial properties have been used since antiquity as preservatives. However, displacement of successhil synthetic products by natural products in preservatives of any category remains to be witnessed. 

The use of BRMs to treat human disease has its origins in the use of bacterial toxins to treat cancer by William B. Coley.73 These early studies resulted in the use of microbi-ally-derived substances such as BCG, Picibanil, carbohydrates from plants or fungi such as Krestin and Lentinan, other products such as Biostim and Broncho-Vaxom, as well as thymic extracts (Table 9.4). However, the lot-to-lot variation in the manufacture of these drugs has dampened enthusiasm. Equally, the focus on MOAs in drug development strategies has also dampened developmental efforts. The particulate nature of some BRMs can also result in pulmonary thrombosis and respiratory distress following i.v. injection. However, BRMs are commonly used to treat bladder cancer and derivatives of natural products are routinely used clinically. 

Building blocks derived from microbial transformations are usually employed as the key units of fluorinated analogs of appropriate natural products or synthetic biologically active materials [42-45]. Among such useful compounds, trifluoromethylated carbohydrates constitute one of the most interesting fields for intensive study. Novel and efficient routes to access a variety of chiral... 

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