Macrolides pharmacologic properties

The purpose of this review is to offer a comprensive survey of the chemistry of lithistid sponges with a particular emphasis to the pharmacological properties and to the mechanisms of action of their metabolites, and to report the total syntheses of representative macrolides and peptides isolated from the sponges belonging to this so fascinating order. 

Tacrolimus, a macrolide derivative, has similar immunosuppressive properties to ciclosporin and has effects on T lymphocytes by inhibiting interleukin-2 production. On a weight basis, tacrolimus is about 100 times more potent than ciclosporin. In view of the outcome of several multicenter trials, it has been used as an alternative to ciclosporin as a baseline regimen for the prophylaxis of renal and liver transplant rejection and in the treatment of acute rejection (SED-13,1130) (SEDA-21, 390) (1). The clinical pharmacology, clinical use, and adverse effects profile of tacrolimus in organ transplantation have been extensively reviewed (2). 

Most of the pharmacologically active macrolides have highly substituted structures as can be seen from the examples shown earlier. However, complexity of the structure is not essential for biological activity and relatively simple macroHdes such as aspergillides 24 and patulolides 25 (Figure 6.10) possess interesting properties that make them worth studying. 

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