Detail of "979-92-0"

Reference

3-Deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells

3-Deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells. Glazer, Robert I.; Knode, Marian C.; Tseng, Christopher K. H.; Haines, David R.; Marquez, Victor E. (Lab. Biol. Chem., Natl. Cancer Inst., Bethesda, MD 20892, USA). Biochem. Pharmacol., 35(24), 4523-7 (English) 1986. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The mechanism of action of the cyclopentenyl analog of 3-deazaadenosine 3-deazaneplanocin A (c3Nep) [102052-95-9] was investigated in the human colon carcinoma cell line HT-29. Upon exposure of cells for 24 h to c3Nep, neplanocin A (Nep) [72877-50-0] or 3-deazaaristeromycin (c3Ari) [58316-88-4], significant toxicity was noted only for Nep, wherein an 87% redn. in viability was produced at 100 mM. C3Nep and c3Ari at 100 mM reduced viability by 34 and 21%, resp. Intracellular levels of S-adenosylhomocysteine (AdoHcy) [979-92-0] were elevated by a 24-h exposure to 100 mM c3Nep, Nep and c3Ari and were 120, 75, and 25 pmol/106 cells, resp. Only Nep was metabolized to an S-adenosylmethionine-like metabolite, and its formation was concn.-related to its cytotoxicity. The half-life for the disappearance of elevated levels of AdoHcy following drug removal was 1.6-2.5 h for all drugs. RRNA and tRNA methylation was inhibited by Nep, but c3Nep and c3Ari inhibited tRNA methylation but not rRNA methylation to a lesser degree. These results demonstrate that c3Nep is a potent inhibitor of AdoHcy synthesis with low cytotoxicity.

Inhibition of protein carboxylmethylation and dopamine autoreceptor functioning

Inhibition of protein carboxylmethylation and dopamine autoreceptor functioning. Saller, Charles F.; Salama, Andre I. (Div. of ICI Americas Inc., Stuart Pharm., Wilmington, DE 19897, USA). Eur. J. Pharmacol., 111(1), 17-22 (English) 1985. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) S-Adenosyl-L-homocysteine (SAH) [979-92-0] (2-100 mM) greatly inhibited protein carboxymethylation (PCM) in rat striatal synaptosomes, but did not alter the ability of apomorphine [58-00-4] and other dopaminergic agonists to inhibit dopamine (DA) [51-61-6] synthesis. SAH (10 mM) also did not significantly alter the ability of either 0.5 or 1.0 mM apomorphine to inhibit DNA release from superfused rat striatal tissue slices, but it did antagonize the response to 5.0 mM apomorphine. The former 2 concns. of apomorphine predominantly affected only DA release, whereas the latter concn. suppressed both DA and acetylcholine [51-84-3] release. The findings are discussed with regard to the possible relation between DA autoreceptor functioning and PCM activity.