Drug discovery immunosuppressive drugs

Studies using free energy calculations for the design and analysis of potential drug candidates are reviewed in section five. The chapters in this section cover drug discovery programs targeting fructose 1,6-bisphosphatase (diabetes), COX-2 (inflammation), SRC SH2 domain (osteoporosis and cancer), HIV reverse transcriptase (AIDS), HIV-1 protease (AIDS), thymidylate synthase (cancer), dihydrofolate reductase (cancer) and adenosine deaminase (immunosuppression, myocardial ischemia). 

In addition, negative dietary correlations can afford clues to drug discovery. Thus, the potent immunosuppressant dammarane triterpenoid 36 was discovered because of epidemiological correlations between the incidence of cancer and the consumption of Palmyrah flour (Borassus flabellifer), a staple for Sri Lankan Tamils.97... 

Volume 32 of Studies in Natural Products Chemistry contains 23 comprehensive articles written by international authorities in various fields of natural product chemistry ranging from immunosuppressant and antimalarial compounds to bioactive substances useful in cancer and neural diseases. It is hoped that the present volume, which is the 32nd of the Series, which I initiated in 1988 will again be of great interest to research scientists and scholars working in the exciting field of new drug discovery. 

Direct site-selective functionalization of natural products is a powerful tool for the discovery of drug candidates because nature provides a rich pool of unique molecular frameworks with diverse biological profiles [32,33], Acylation of a particular hydroxy group among multiple hydroxy groups in polyol natural products has been well studied by means of enzymatic protocol [34], For example, acylation of rapamycin, an immunosuppressive agent, took place at C(42)-OH selectively in the presence of PSL-C to provide an anticancer agent, temsirolimus (Scheme 13) [35]. Inspired by these achievements, extensive efforts have been devoted to develop the non-enzymatic counterparts toward site-selective functionalization of polyol natural products [4],... 

Originally developed for chemotherapy, azathioprine is used today mainly as an immunosuppressive agent and rarely as an antineoplastic drug. It was introduced as an immunosuppressive agent by a British pioneer of tissue transplantation, Roy Caine. Azathioprine was used to prevent rejection after tissue transplantation as a replacement for 6-mercaptopurine because it was less toxic. In addition to tissue transplantation, it is also used for rheumatoid arthritis and Crohn s disease. Azathioprine is a prodrug which in the body is converted to its active metabolites 6-mercaptopurine and 6-thioinosinic acid. Until the discovery of cyclosporine, azathioprine in combination with steroids was the standard treatment to prevent rejection after tissue transplantation. 

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