Antitumor activity and mechanism of action of the marine compound girodazole

Girodazole, a new marine compound has been isolated from the sponge Pseudaxinyssa cantharella. Girodazole is active in vivo on several murine grafted tumors including leukemias (P388, L1210, i.p./i.p.) and solid tumors (MA 16/C mammary adenocarcinoma, M5076 histiocytosarcoma, s.c./i.v.). In addition...

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Bibliographic Details
Published in:Investigational new drugs 1991-08, Vol.9 (3), p.233-244
Main Authors: LAVELLE, F, ZERIAL, A, FIZAMES, C, RABAULT, B, CURAUDEAU, A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Division - drug effects
Chemotherapy
DNA, Neoplasm - biosynthesis
Humans
Imidazoles - pharmacology
Leukemia P388 - drug therapy
Leukemia P388 - genetics
Leukemia P388 - metabolism
Medical sciences
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Neoplasm Proteins - biosynthesis
Neoplasm Transplantation
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - genetics
Neoplasms, Experimental - metabolism
Pharmacology. Drug treatments
Propanolamines - pharmacology
Protein Biosynthesis - drug effects
Rabbits
RNA, Neoplasm - biosynthesis
Transcription, Genetic - drug effects
Tumor Cells, Cultured
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Summary:Girodazole, a new marine compound has been isolated from the sponge Pseudaxinyssa cantharella. Girodazole is active in vivo on several murine grafted tumors including leukemias (P388, L1210, i.p./i.p.) and solid tumors (MA 16/C mammary adenocarcinoma, M5076 histiocytosarcoma, s.c./i.v.). In addition, girodazole has identical cytotoxic properties in vitro on P388 and P388/DOX cells and retains antitumor activity in vivo on P388/DOX. Girodazole has a unique chemical structure different from those of known anticancer agents and of new compounds undergoing clinical trials. Biochemical studies indicate that girodazole inhibits protein synthesis during the elongation/termination steps. Toxicological studies have been done in mice and in dogs and did not reveal any major toxic effect which could preclude administration in patients. Girodazole is now undergoing phase I clinical studies.
ISSN:0167-6997
1573-0646
DOI:10.1007/bf00176976