Inhibitory effects of Ge-132 (carboxyethyl germanium sesquioxide) derivatives on enkephalin-degrading enzymes.
Twenty-eight species of carboxyethyl germanium sesquioxide (Ge-132) derivatives were examined for their inhibitory effects on enkephalin-degrading enzymes that were purified from monkey brain, the longitudinal muscle layer of bovine small intestine, and human cerebrospinal fluid (CSF). A series of the sulfurized Ge-132 derivatives showed strong inhibition of these purified enzymes. The most effective ones were Ge-014 and Ge-107, which showed IC50 values of 60 and 100 micrograms/ml, respectively, for dipeptidylcarboxypeptidase from the longitudinal muscle layer. They also exhibited inhibitory activity against aminopeptidase from human CSF, the IC50 values being 450 and 440 micrograms/ml, respectively. Furthermore, these compounds showed inhibition of dipeptidylaminopeptidase from monkey brain and the longitudinal muscle layer of bovine small intestine. These compounds are expected to have analgesic effects due to their inhibition of the degradation of endogenous opioid peptides.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002417:Cattle; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D010450:Endopeptidases; D004745:Enkephalins / Q000378:metabolism; D005857:Germanium / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology; D009942:Organometallic Compounds / Q000494:pharmacology*; D011422:Propionates; D011480:Protease Inhibitors
D000700:Analgesics; D004745:Enkephalins; D006146:Guanidines; D009942:Organometallic Compounds; D011422:Propionates; D011480:Protease Inhibitors; D005857:Germanium; C066750:propagermanium; C040038:arphamenine A; C040039:arphamenine B; D002268:Carboxypeptidases; D010450:Endopeptidases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C020071:dipeptidyl carboxypeptidase