Chemistry Reference
In-Depth Information
toxicity, but its 2-morpholinoethylester was approved as a new immunosuppres-
sant for kidney and heart transplantation (1). This compound acts as an inhibitor
of inosine monophosphate dehydrogenase, which is rate limiting in the synthesis
of guanosine nucleotides and therefore affects T- and B-lymphocytes that are
dependent on this pathway.
Myriocin (
87
) (ISP-1, thermozymocidine) is an acyclic diterpene that was
shown to be 10- to 100-fold more potent than cyclosporine A. This compound
is produced by
Isaria sinclairii, Myriococcum albomyces
and
Mycelia sterilia
(60). Myriocin potently inhibits the enzyme serine palmitoyltransferase, thereby
decreasing sphingolipid content. Myriocin shows high toxicity and low solubility
compared with cyclosporine A. Thus, this compound has been chemically mod-
ified to create a less toxic drug named fingolimod (
88
). In addition, fingolimod
has been approved recently for the treatment of multiple sclerosis (60). It is the
first orally administered disease-modifying treatment for multiple sclerosis to be
approved in the United States, and it disrupts the disease's attack on the central
nervous system (CNS) through a unique mechanism.
3.10.3
Immunosuppressive Macrolides
Tacrolimus (
89
) and rapamycin (
90
) are macrolides linked to amino acids that
were isolated from
Streptomyces tsukubaensis
and
S. hygroscopicus
, respectively.
87
88
89
