Year: 1993
Type: article
Abstract: 3-31-12 ShinroSpergualin (SG) is an antitumor and immunosuppressive antibiotic isolated from the culture filtrates of Bu&!l u. r h m s BMG162-aF2 and has been determined to be ( -)-( I5S)-l-amino-19-guanidino-l1,15-dihydroxy-4,9,12-triazanonadecane-l0,13dione.'JIts total synthesis has been accomplished3 and 15-deoxysperguahn (DSG) has been derived chemically from SG.' SG consists of (3S)-7-guanidino-3-hydroxyheptanoic acid, a-hydroxyglycine, and spermidine, and is unstable owing to the presence of an a-hydroxyglycine moiety, which is an unusual hemiaminal structure, at the 10-12 position of the molecule.Consequently, in basic or acidic aqueous solution, SG hydrolyzes gradually into a (3s)-7-guanidino-3-hydroxyheptanoic acid amide and a hydrate of glyoxyloylspermidine, as shown in FIGURE 1.Three functional portions-the 7-guanidino-3-hydroxyheptanoic acid, ahydroxy-glycine, and spermidine moieties in SG-are postulated to play an important role in the manifestation of its biological activities.In order to confirm the above hypothesis, to improve the compound's stability, and to obtain analogues with high biological activities, more than 400 analogues of SG were synthesized and their structure-activity relationships examined. ASSAY METHODS An titumor ActivieTwo to ten male BDFl mice (5 weeks old) were inoculated intraperitoneally (i.p.) with lo5 cells of L1210 (IMC), a subline of L1210, and injected (i.p.) with the test compound once a day for 6 days starting from the day of the tumor inoculation.Antitumor activity was expressed as the T/C (%) value calculated on the basis of the mean survival period at 30 days after the tumor inoculation according to the equation: 123
Authors: KENJI MAEDA, YOSHIHISA UMEDA, TETSUSHI SAINO
Language: English
Subfield: Applied Microbiology and Biotechnology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2121663134