1.0 2011-09-21 01:52:58 UTC 2015-07-21 06:59:40 UTC FDB029273 S-(9-Deoxy-delta9,12-PGD2)-glutathione The major dehydration product of prostaglandin D2, 9-deoxy-d9,d12(E)-prostaglandin D2, is a potent cytotoxic compound. Like other cytotoxic prostaglandins, this compound possesses an α,β-unsaturated ketone group to which cytotoxic activity has been attributed. This prostaglandin was found to readily conjugate with glutathione (GSH) in vitro. When 9-deoxy-d9,d12(E)-prostaglandin D2 was incubated with Chinese hamster ovary or hepatoma tissue culture cells, it was rapidly taken up and was recovered in the cell lysate primarily as a GSH conjugate in which the keto group at C-11 and the Δ12 double bond had been reduced. Identification of the GSH conjugate was accomplished by analysis by fast atom bombardment mass spectrometry following purification by high performance liquid chromatography. This GSH conjugate and its cysteinylglycinyl and cysteinyl metabolites were also identified in the cell culture medium. 9-Deoxy-d9,d12(E)-prostaglandin D2 inhibited cell proliferation of these two cell lines in a concentration dependent manner. Depletion of intracellular glutathione by treatment with diethyl maleate and buthionine sulfoximine decreased the amount of intracellular conjugated prostaglandin recovered, and significantly enhanced the antiproliferative effect of 9-deoxy-d9-d12(E)-prostaglandin D2 on the growth of these cell lines in a concentration dependent fashion. Intracellular GSH may modulate the antiproliferative activity of 9-deoxy-Δ9,Δ12(E)-prostaglandin D2 and, possibly, of other cytotoxic prostaglandins. [HMDB] C30H47N3O10S 641.773 641.298215429 (5Z)-7-[(1S,2E)-5-{[(2R)-2-[(4R)-4-amino-4-carboxybutanamido]-2-[(carboxymethyl)carbamoyl]ethyl]sulfanyl}-2-[(3S)-3-hydroxyoctylidene]-3-oxocyclopentyl]hept-5-enoic acid (5Z)-7-[(1S,2E)-5-{[(2R)-2-[(4R)-4-amino-4-carboxybutanamido]-2-(carboxymethylcarbamoyl)ethyl]sulfanyl}-2-[(3S)-3-hydroxyoctylidene]-3-oxocyclopentyl]hept-5-enoic acid CCCCC[C@H](O)C\C=C1/[C@H](C\C=C/CCCC(O)=O)C(CC1=O)SC[C@H](NC(=O)CC[C@@H](N)C(O)=O)C(=O)NCC(O)=O InChI=1S/C30H47N3O10S/c1-2-3-6-9-19(34)12-13-20-21(10-7-4-5-8-11-27(37)38)25(16-24(20)35)44-18-23(29(41)32-17-28(39)40)33-26(36)15-14-22(31)30(42)43/h4,7,13,19,21-23,25,34H,2-3,5-6,8-12,14-18,31H2,1H3,(H,32,41)(H,33,36)(H,37,38)(H,39,40)(H,42,43)/b7-4-,20-13+/t19-,21-,22+,23-,25?/m0/s1 RPHLHZIDWIFTII-RJQMMLODSA-N belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds. Oligopeptides Organic compounds Organic acids and derivatives Carboxylic acids and derivatives Amino acids, peptides, and analogues Aliphatic homomonocyclic compounds Alpha amino acid amides Amino acids Carbonyl compounds Carboxylic acids Cyclic alcohols and derivatives Cyclopentanols Cysteine and derivatives D-alpha-amino acids Dialkylthioethers Gamma-glutamyl peptides Glutamine and derivatives Hydrocarbon derivatives Monoalkylamines N-acyl amines N-acyl-alpha amino acids Organic oxides Organopnictogen compounds Secondary carboxylic acid amides Sulfenyl compounds Tricarboxylic acids and derivatives Alcohol Aliphatic homomonocyclic compound Alpha-amino acid Alpha-amino acid amide Alpha-amino acid or derivatives Alpha-oligopeptide Amine Amino acid Amino acid or derivatives Carbonyl group Carboxamide group Carboxylic acid Cyclic alcohol Cyclopentanol Cysteine or derivatives D-alpha-amino acid Dialkylthioether Fatty acyl Fatty amide Gamma-glutamyl alpha peptide Glutamine or derivatives Hydrocarbon derivative N-acyl-alpha amino acid or derivatives N-acyl-alpha-amino acid N-acyl-amine N-substituted-alpha-amino acid Organic nitrogen compound Organic oxide Organic oxygen compound Organonitrogen compound Organooxygen compound Organopnictogen compound Organosulfur compound Primary aliphatic amine Primary amine Secondary alcohol Secondary carboxylic acid amide Sulfenyl compound Thioether Tricarboxylic acid or derivatives Solid logp -1.05 ALOGPS logs -4.69 ALOGPS solubility 1.30e-02 g/l ALOGPS logp -0.92 ChemAxon pka_strongest_acidic 1.81 ChemAxon pka_strongest_basic 9.31 ChemAxon iupac (5Z)-7-[(1S,2E)-5-{[(2R)-2-[(4R)-4-amino-4-carboxybutanamido]-2-[(carboxymethyl)carbamoyl]ethyl]sulfanyl}-2-[(3S)-3-hydroxyoctylidene]-3-oxocyclopentyl]hept-5-enoic acid ChemAxon average_mass 641.773 ChemAxon mono_mass 641.298215429 ChemAxon smiles CCCCC[C@H](O)C\C=C1/[C@H](C\C=C/CCCC(O)=O)C(CC1=O)SC[C@H](NC(=O)CC[C@@H](N)C(O)=O)C(=O)NCC(O)=O ChemAxon formula C30H47N3O10S ChemAxon inchi InChI=1S/C30H47N3O10S/c1-2-3-6-9-19(34)12-13-20-21(10-7-4-5-8-11-27(37)38)25(16-24(20)35)44-18-23(29(41)32-17-28(39)40)33-26(36)15-14-22(31)30(42)43/h4,7,13,19,21-23,25,34H,2-3,5-6,8-12,14-18,31H2,1H3,(H,32,41)(H,33,36)(H,37,38)(H,39,40)(H,42,43)/b7-4-,20-13+/t19-,21-,22+,23-,25?/m0/s1 ChemAxon inchikey RPHLHZIDWIFTII-RJQMMLODSA-N ChemAxon polar_surface_area 233.42 ChemAxon refractivity 164.95 ChemAxon polarizability 68.49 ChemAxon rotatable_bond_count 23 ChemAxon acceptor_count 11 ChemAxon donor_count 7 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Specdb::MsMs 313921 Specdb::MsMs 313922 Specdb::MsMs 313923 Specdb::MsMs 359524 Specdb::MsMs 359525 Specdb::MsMs 359526 Specdb::MsMs 2743735 Specdb::MsMs 2743736 Specdb::MsMs 2743737 Specdb::MsMs 2934438 Specdb::MsMs 2934439 Specdb::MsMs 2934440 Specdb::NmrOneD 151990 Specdb::NmrOneD 151991 Specdb::NmrOneD 151992 Specdb::NmrOneD 151993 Specdb::NmrOneD 151994 Specdb::NmrOneD 151995 Specdb::NmrOneD 151996 Specdb::NmrOneD 151997 Specdb::NmrOneD 151998 Specdb::NmrOneD 151999 Specdb::NmrOneD 152000 Specdb::NmrOneD 152001 Specdb::NmrOneD 152002 Specdb::NmrOneD 152003 Specdb::NmrOneD 152004 Specdb::NmrOneD 152005 Specdb::NmrOneD 152006 Specdb::NmrOneD 152007 Specdb::NmrOneD 152008 Specdb::NmrOneD 152009 Specdb::CMs 21555 Specdb::CMs 617932 Specdb::CMs 617933 Specdb::CMs 617934 Specdb::CMs 617935 Specdb::CMs 617936 Specdb::CMs 617937 Specdb::CMs 617938 Specdb::CMs 617939 Specdb::CMs 617940 Specdb::CMs 617941 Specdb::CMs 617942 Specdb::CMs 617943 Specdb::CMs 617944 Specdb::CMs 617945 Specdb::CMs 617946 Specdb::CMs 617947 Specdb::CMs 617948 Specdb::CMs 617949 Specdb::CMs 617950 Specdb::CMs 617951 Specdb::CMs 617952 Specdb::CMs 617953 Specdb::CMs 617954 Specdb::CMs 617955 HMDB13058