Natural products antimalarial agents

Nature has been a potential source of therapeutic agents for thousands of years. An impressive number of modem dmgs have been derived from natural sources. Over the last century, a number of top selling dmgs have been developed from natural products. Anticancer dmg vincristine from Vinca rosea, narcotic analgesic morphine from Papaver somniferum, antimalarial dmg artemisinin from Artemisia annua, anticancer dmg Taxol from Taxus brevifolia and antibiotic peniciUins from Penicillium ssp. are just a few examples. 

All the reactions reported in this section deal with modification of substituents of dioxocins, analogues of the natural antimalarial agent yingzhaosu A, possessing antimalarial activity or utilized in the total synthesis of the natural product. 

NATURAL PRODUCTS IN E. Isolation of active compounds H. Antimalarial agents... 

Batista, R. de Jesus Silva Junior, A. de Oliveira, A., Plant-derived antimalarial agents New leads and efficient phytomedicines. Part II. Non-alkaloidal natural products, Mo/ecu/ex, 2009, 14, 3037-3072. 

The study of natural products, or Nature s Combinatorial Library , has had a long history as a source of drugs, and plants have historically been at the forefront of natural product drug discovery. In the anticancer area, for example, vinblastine and vincristine, etoposide, paclitaxel (Taxol), docetaxel, topotecan, and irinotecan, among others, are all plant-derived natural products or modified versions of plant compounds, while antimalarial therapy would be much poorer without quinine and artemisinin and the drugs derived from these plant products. This chapter provides an overview of the major medicinal agents that are themselves natural products isolated from plants or are chemical modifications of such lead compounds. It covers the therapeutic areas of cancer, HIV, malaria, cardiovascular, and central nervous system (CNS) diseases. Natural plant products have also made contributions in areas such as immunomodulatory and antibiotic activities," and the reader is referred to the cited reviews for information on these areas. 

Marine natural products are even more poorly characterized than terrestrial plants but are no less diverse. Chemical compounds with unique and significant biological activities are being discovered with increasing frequency as this immense resource is explored. Since many of these compounds are reported to possess antiprotozoal activities, (106-108) the marine environment may be reasonably expected to yield potential antimalarial agents. 

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... 

As a privileged fragment, quinoline is a ubiquitous subunit in many quinoline-containing natural products with remarkable biological activities [37], Members of this family have wide applications in medicinal chemistry, being used as antimalarial, anti-inflammatory, antiasthmatic, antibacterial, anti-hypertensive, and tyrosine kinase-inhibiting agents [38, 39],... 

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