الفهرس | Only 14 pages are availabe for public view |
Abstract Cancer and infectious diseases cause millions of deaths worldwide per year, and the number of affected persons and deaths are increasing steadily. The development of new chemotherapeutic agents for the treatment of cancer and microbial infections is still urgently needed to help to ensure the availability of new drug candidates to feed the preclinical pipeline. This will help to surmount current issues arising from the drawbacks of current drugs such as low efficacy, significant side effects and resistance. In this context, plants are still an important resource for the discovery of new drugs. Natural products have recently drawn renewed interests and attentions as the seed of novel medicines. However, availability of such natural products from nature tends to be severely limited. In order to develop novel medicines from natural products, sufficient amounts of compounds need to be provided for derivatization and biological testing. One of the goals of our thesis is to establish practical synthetic route for the natural products of medicinal importance. In addition, a variety of derivatives of the natural products will be synthesized for biological testing. Many naturally occurring compounds, including the minor alkaloid neocryptolepine 1 and major alkaloid cryptolepine 2, were isolated from the roots of the West African climbing shrub Cryptolepis sanguinolenta (Figure 1), a traditional herb used in folk medicine for the treatment of malaria. Both of the two tetracyclic heteroaromatic compounds are linearly fused indoloquinolines and exhibit a wide scope of biological activity. Therefore, we selected neocryptolepine 1 as the lead compound for the development of a new drug because of its lower cytotoxic activity compared to cryptolepine 2 towards the DNA intercalation, in addition natural product alkaloids are known for their broad spectrum of pharmacological activity. |