Girolline (Girodazole)

Molecular Weight: 190.631 g/mol
Molecular Formula: C₆H₁₁ClN₄O

Source: First reported from the sponge Pseudaxinyssa (= Cymbastela) cantharella (PORIFERA)
Activity: protein synthesis inhibitor
Status: Clinical trials discontinued (see below)

Compared to many natural products, the structure of this substituted imidazole is simple.

Girolline was reported to inhibit protein synthesis in eukaryotic target cells. The compound was of interest because it inhibited protein synthesis at the termination steps of the process rather than at the initiation or chain elongation steps like other known inhibitor compounds (e.g., emitine, homoharringtonine, anguidine).

Although Girolline was moved through to Phase I clinical trials, the trials were stopped when some patients receiving the drug demonstrated significant hypertension as a side-effect.

The simple structure of the compound facilitated the production of a modified synthetic analog, in the hope that the negative side effects could be eliminated. The resulting synthetic compound was shown not to have the bioactivity of the natural product, however.

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts (Girolline) - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts (Girodazole) - [ LINK ]

References

Newman DJ, and GM Cragg. 2004. Advanced Preclinical and Clinical trials of natural Products and Related Compounds from marine Sources. Current Medicinal Chemistry 11:1693-1713.