Synthesis and antibacterial activity of egonol derivatives

Synthesis of egonol derivatives, 5-(3'-chloropropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 1, 5-(3'-bromopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propanal 3, 5-(3'-iodopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 4, 5-[3-(3'-bromopropyloxy) propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propyloleate 7, 5-[3'-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylbenzoate 10, 5-[3'-hydroxypropyl]-7-methoxy-3-nitro-2-(3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli are reported. The starting material egonol 5-[3'-(hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated from seeds of Styrax officinalis L. The structural elucidication of these compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC, COSY) and LCMS spectroscopic data. While egonol and some synthesised new compounds show similar antibacterial activity and MIC values against S. aureus, B. subtilis, C. albicans and E. coli, other new derivatives show different activity against S. aureus, B. subtilis, C. albicans and E. coli.     

Inhibitory effect on NO production of phenolic compounds from Myristica fragrans

Three new phenolics: ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (1), ((7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl)benzene-2,4-diol (2) and ((8R,8'S)-7-(4-hydroxy-3-methoxyphenyl)-8'-methylbutan-8-yl)-3'-methoxybenzene-4',5'-diol (3), along with four known compounds (4-7) were isolated from the seeds of Myristica fragrans. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells.     

Alpha-pyrones and a 2(5H)-furanone from Hyptis pectinata

Three pyrones and a 2(5H)-furanone, designated pectinolides D-G, have been isolated from the dichloromethane extract of Hyptis pectinata. The metabolites were characterized on the basis of 1D and 2D NMR spectroscopic techniques. The pyrones were identified as 6S-[3S,6S-(diacetoxy)-5R-hydroxy-1Z-heptenyl]-5S-hydroxy-5,6-dihydro-2H-pyran-2-one (1)- pectinolide D, 6S-[3S,5R,6S-(triacetoxy)-1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (2)- pectinolide E and 6S-[3S,5R,6S-(triacetoxy)-1Z-heptenyl]-5S-acetoxy-4R-methoxy-3,4,5,6-tetrahydro-4H pyran-2-one (3)- pectinolide F. The furanone was identified as [2'Z,5(1')Z] 5-(4'S,6'R,7'S-triacetoxy-2-octenylidene)-2(5H)-furanone (4)-pectinolide G.     

Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids

Eleven homoisoflavonoids and two xanthones were isolated and characterized from the bulbs of Ledebouria graminifolia. Five of the homoisoflavonoids are new compounds and were identified as: 5-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-6,7-dimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5,7,8-trimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-3',4',7-trimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one, 5,7-dihydroxy-3',4'-dimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one. Structures were elucidated by extensive 1D, and 2D NMR spectroscopy and HRMS. A method for tissue culture was developed and the bulbs of mature plants were found to contain all the compounds isolated from the wild specimens of L. graminifolia.     

Minor groove orientation for the (1S,2R,3S,4R)-N2- [1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[a]anthracenyl)]-2'-deoxyguanosyl adduct in the N-ras codon 12 sequence

The conformation of the trans-anti-(1S,2R,3S,4R)-N(2)-[1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[a]anthracenyl)]-2'-deoxyguanosyl adduct in d(G(1)G(2)C(3)A(4)G(5)X(6)T(7)G(8)G(9)T(10)G(11)).d(C(12)A(13)C(14)C(15)A(16)C(17)C(18)T(19)G(20)C(21)C(22)), bearing codon 12 of the human N-ras protooncogene (underlined), was determined. This adduct had S stereochemistry at the benzylic carbon. Its occurrence in DNA is a consequence of trans opening by the deoxyguanosine amino group of (1R,2S,3S,4R)-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracenyl-3,4-diol. The resonance frequencies, relative to the unmodified DNA, of the X(6) H1' and H6 protons were shifted downfield, whereas those of the C(18) and T(19) H1', H2', H2' ', and H3' deoxyribose protons were shifted upfield. The imino and amino resonances exhibited the expected sequential connectivities, suggesting no interruption of Watson-Crick pairing. A total of 426 interproton distances, including nine uniquely assigned BA-DNA distances, were used in the restrained molecular dynamics calculations. The refined structure showed that the benz[a]anthracene moiety bound in the minor groove, in the 5'-direction from the modified site. This was similar to the (+)-trans-anti-benzo[a]pyrene-N(2)-dG adduct having S stereochemistry at the benzylic carbon [Cosman, M., De Los Santos, C., Fiala, R., Hingerty, B. E., Singh, S. B., Ibanez, V., Margulis, L. A., Live, D., Geacintov, N. E., Broyde, S., and Patel, D. J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918]. It differed from the (-)-trans-anti-benzo[c]phenanthrene-N(2)-dG adduct having S stereochemistry at the benzylic carbon, which intercalated in the 5'-direction [Lin, C. H., Huang, X., Kolbanovskii, A., Hingerty, B. E., Amin, S., Broyde, S., Geacintov, N. E., and Patel, D. J. (2001) J. Mol. Biol. 306, 1059-1080]. The results provided insight into how PAH molecular topology modulates adduct structure in duplex DNA.     

Antibacterial and antifungal flavanones from Eysenhardtia texana

An activity-guided fractionation of a methanol-dichloromethane extract obtained from the aerial parts of Eysenhardtia texana led to the isolation of two novel antibacterial and antifungal flavanones together with a known flavanone. Their structures were established as 4',5,7-trihydroxy-8-methyl-6-(3-methyl-[2-butenyl])-(2S)-flavanone, 4',5,7-trihydroxy-6-methyl-8-(3-methyl-[2-butenyl])-(2S)-flavanone and 4',5-dihydroxy-7-methoxy-6-(3-methyl-[2-butenyl])-(2S)-flavanone on the basis of their UV, 1D and 2D-NMR spectra.     

Derivatives of methanopterin, a coenzyme involved in methanogenesis

Degradational studies of methanopterin, a coenzyme involved in methanogenesis, are reported. The results of these studies are in full accordance with the proposed structure of methanopterin as N-[1'-(2'-amino-4'-hydroxy-7' -methyl-6'-pteridinyl)ethyl]-4-[2', 3', 4', 5'-tetrahydroxypent-1'-yl(5'-1' )O-alpha-ribofuranosyl-5'-phosphoric acid] aniline in which the phosphate group is esterified with alpha-hydroxyglutaric acid. Acid hydrolysis of methanopterin cleaved the 5'----1' glycosidic bond and yielded a 'hydrolytic product' which was identified as N-[1'-(2'-amino-4'-hydroxy-7' -methyl-6'-pteridinyl)ethyl]-4-[2', 3', 4', 5'-tetrahydroxypent-1'-yl]aniline. Alkaline permanganate oxidation of methanopterin yielded 7-methylpterin-6-carboxylic acid. Catalytic (or enzymatic) hydrogenation of methanopterin gave a mixture of 6-ethyl-7-methyl-7,8-dihydropterin, 6-ethyl-7-methylpterin and a third compound, named methaniline which was identified as 4-[2', 3', 4', 5'-tetrahydroxypent-1'-yl(5'----1')O-alpha -ribofuranosyl-5'-phosphoric acid]aniline, in which the phosphate group is esterified with alpha-hydroxyglutaric acid. Methanosarcina barkeri contains a closely related coenzyme called sarcinapterin, which was identified as a L-glutamyl derivative of methanopterin, where the glutamate moiety is attached to the alpha-carboxylic acid group of the alpha-hydroxyglutaric acid moiety of methanopterin via an amide linkage.     

Benzofurans and another constituent from seeds of Styrax officinalis

The benzofuran constituents of the seeds of Styrax officinalis were investigated. From the hexane extract, two new constituents named 5-(3"benzoyloxypropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (5) and 4-[3"-(1c-methylbutanoyloxy)propyl]-2-methoxy-(3',4'-methylenedioxyphenyl)-1a, 5b-dihydrobenzo-[3,4]-cyclobutaoxirene (6) were isolated together with four known compounds, 5-[3"-(1c-methylbutanoyloxy)propyl]-7-methoxy-2-(3',4'-dimethoxyphenyl)-benzofuran (4), 5-[3"-(1c-methylbutanoyloxy)propyl]-7- methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran (3), 5-(3"-acetoxypropyl)-7-methoxy2-(3',4'-methylenedioxphenyl)-benzofuran (2) and 5-(3"-hydroxypropyl)-7-methoxy-2-(3',4'-met hylenedioxyphenyl)-benzofuran (1). Although the compounds 1, 2, and 3 have been isolated previously from the seeds of Styrax obassia, this is the first record of their isolation from seeds of Styrax officinalis. The structures of the isolated compounds were established by 1D- and 2D-NMR (HMBC, HMQC, COSY), FABMS and high-resolution ESI FTMS.     

Geranylated flavanones from the secretion on the surface of the immature fruits of Paulownia tomentosa

Chemical investigation of the methanol extract of the viscous secretion on the surface of immature fruits of Paulownia tomentosa furnished nine geranylated flavanones, 6-geranyl-5,7-dihydroxy-3',4'-dimethoxyflavanone (1), 6-geranyl-3',5,7-trihydroxy-4'-methoxyflavanone (2), 6-geranyl-4',5,7-trihydroxy-3',5'-dimethoxyflavanone (3), 6-geranyl-4',5,5',7-tetrahydroxy-3'-methoxyflavanone (4), 6-geranyl-3,3',5,7-tetrahydroxy-4'-methoxyflavanone (5), 4',5,5',7-tetrahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]-3'-methoxyflavanone (6), 3,3',4',5,7-pentahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]flavanone (7), 3,3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone (8), and 3,4',5,5',7-pentahydroxy-3'-methoxy-6-(3-methyl-2-butenyl)flavanone (9), along with six known geranylated flavanones. Among these, compounds 4, 6-9 and the known 6-geranyl-3',4',5,7-tetraahydroxyflavanone (diplacone), 6-geranyl-3,3',4',5,7-pentahydroxyflavanone (diplacol) and 3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone showed potent radical scavenging effects towards DPPH radicals.     

Non-glycosidic iridoids from Cymbaria mongolica

Six non-glycosidic iridoids, i.e. (1R,4S,4aS,7S,7aS)-7-hydroxyl-4-hydroxy- methyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta[e]pyran-3-one (1), (1S,4R,4aS,7S,7aS)-7-hydroxyl-4-hydroxymethyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta[e]pyran-3-one (2), (1R,4R,4aS,7S,7aS)-7-hydroxyl-4-hydroxy-methyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta[e]pyran-3-one (3), (1R, 4R, 4aS, 7aS)-4,7-dihydroxymethyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta-6-ene[e]pyran-3-one (4), (1R, 4R, 4aS, 7aS)-4,7-dihydroxymethyl-1-hydroxyl-1,4,4a, 7a-tetrahydrocyclopenta-6-ene[e]pyran-3-one (5), (1R, 4S, 4aS, 7aS)-4,7-dihydroxy-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta-6-ene[e]pyran-3-one (6), as well as five known non-glycosidic iridoids mussaenin A (7), gardendiol (8), isoboonein (9), 4-epi-alyxialactone (10) and rehmaglutin D (11) have been isolated from the Chinese medicinal plant Cymbaria mongolica. Their structures were elucidated by spectroscopic methods. These compounds exhibit significant antitumor and antibacterial activity.     

Iridoid glucosides and flavones from the aerial parts of Avicennia marina

Two new iridoid glucosides, namely, 2'-O-[(2E,4E)-5-phenylpenta-2,4-dienoyl]mussaenosidic acid (1; mussaenosidic acid = [1S-(1alpha,4aalpha,7alpha,7aalpha)]-1-(beta-D-glucopyranosyloxy)-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carboxylic acid) and 2'-O-(4-methoxycinnamoyl)mussaenosidic acid (2), were isolated from the aerial parts of the mangrove plant Avicennia marina. Beside that, one known iridoid glucoside, 2'-O-coumaroylmussaenosidic acid (3) and four known flavones (flavone = 2-phenyl-4H-1-benzopyran-4-one) including 4',5-dihydroxy-3',7-dimethoxyflavone (4), 4',5-dihydroxy-3',5',7-trimethoxyflavone (5), 4',5,7-trihydroxyflavone (6), and 3',4',5-trihydroxy-7-methoxyflavone (7) were also isolated and identified. The structures of these compounds were elucidated by NMR spectroscopy and by low- and high-resolution mass spectrometry. The chemotaxonomic significance of these findings was discussed. In addition, each isolated compound was evaluated for the ability of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical-scavenging activity.     

Synthesis and characterization of 6-O-beta-lactosyl-alpha,beta-lactoses, 1-O-(6-O-beta-lactosyl-beta-lactosyl)-(R,S)-glycerols, and 4,6-di-O-beta-D-galactopyranosyl-alpha,beta-D-glucoses.

1,2,3,2',3',4',6'-Hepta-O-acetyl-beta-lactose (4) was coupled with 2,3,6,2',3',4',6'-hepta-O-acetyl-alpha-lactosyl bromide (7) in the presence of Hg(CN)2 to afford 1,2,3,2',3',4',6'-hepta-O-acetyl-6-O-(2,3,6,2',3',4',6'-hepta-O-acetyl-b eta- lactosyl)-beta-lactose (11) which, upon O-deacetylation, gave 6-O-beta-lactosyl-alpha,beta-lactoses (64% from 4). In contrast, the reaction of 7 with benzyl 2,3,2',3',4',6'-hexa-O-acetyl-beta-lactoside in the presence of Hg(CN)2 produced 3,6,2',3',4',6'-hexa-O-acetyl-1,2-O- (2,3,2',3',4',6'-hexa-O-acetyl-1-O-benzyl-beta-lactos-6-yl orthoacetyl)-alpha-lactose (63%) and 3,6,2',3',4',6'-hexa-O-acetyl-1,2-O-(1- cyanoethylidene)-alpha-lactose (27%). The glycosidation of 4 using 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide in the presence of Hg(CN)2 afforded, after deprotection, 4,6-di-O-beta-D-galactopyranosyl-alpha,beta-D-glucoses (66%). The reaction of 11 with 1,2-di-O-benzyl-(R,S)-glycerols and trimethylsilyl trifluoromethanesulfonate yielded, after deprotection, 1-O-(6-O-beta-lactosyl-beta-lactosyl)-(R,S)-glycerols (18%). Under the same coupling conditions 11 reacted with 2-O-benzylglycerol to form 3-O-acetyl-2-O-benzyl-1-O-[2',3',4',6'-hexa-O-acetyl-6-O-(2,3,6,2',3',4' ,6'- hepta-O-acetyl-beta-lactosyl)-beta-lactosyl]-(R,S)-glycerols (16%).     

除臭大蒜口服液的GC／MS分析

应用GC/MS联用技术,对除臭大蒜口服液进行了检测,定性鉴定了25种含硫有机化合物。二烯丙基硫醚、甲基烯丙基三硫醚、3-乙烯基-1,2-二硫杂-5-环己烯、2-乙烯基-1,3-二硫杂-5-环己烯和二烯丙基三硫醚是主要组分;二烯丙基四硫醚、烯丙基四硫化氢、2-和3-(2’,3’-二硫杂-5’-己烯基)-3,4-二氢-2H-噻喃、2-(2’-[3’,4’-二氢-2H噻喃基])-1,3-二硫杂-5-环己烯和3-(2’-[3’,4’-二氢-2H-噻喃基])-1,2-二硫杂-5-环己烯是次要组分。最后4种次要组分在大蒜油和大蒜口服液中的鉴定在国内尚属首次。     

Stereochemistry and mechanism of reactions catalyzed by tryptophanase Escherichia coli.

Several beta replacement and alpha,beta elimination reactions catalyzed by tryptophanase from Escherichia coli are shown to proceed stereospecifically with retention of configuration. These conversions include synthesis of tryptophan from (2S,3R)- and (2s,3s)-[3(-3H)]serine in the presence of indole, deamination of these serines in D2O to pyruvate and ammonia, and cleavage of (2S,3R)-and (2S,3S)-[3(-3H)]tryptophan in D2O to indole, pyruvate, and ammonia. A coupled reaction with lactate dehydrogenase was used to trap the stereospecifically labeled [3-H,2H,3H]pryuvates as lactate, which was oxidized to acetate for chirality analysis of the methyl group. During deamination of tryptophan there is significant intramolecular transfer of the alpha proton of the amino acid to C-3 of indole. To determine the exposed face of the cofactor.substrate complex on the enzyme surface and to analyze its conformational orientation, sodium boro[3H]hydride was used to reduce tryptophanase-bound alaninepyridoxal phosphate Schiff's base. Degradation of the resulting pyridoxylalanine to (2S)-[2(-3H)]alanine and (4'S)-[4'(-3H)]pyridoxamine demonstrates that reduction occurs from the exposed si face at C-4' of the complex and that the ketimine double bond is trans.     

Affinity modification of Escherichia coli ribosomes with 2',3'-O-[4-(N-2-chloroethyl)-N-methylamino]-benzylidene derivative of AUGU3 in the 70S initiation complexes

Affinity labelling of the Escherichia coli ribosomes with the 2',3'-O-[4-(N-(2-chloroethyl)-N-methylamino]benzylidene derivative of AUGU3(AUGU3[14C]CHRCl) has been studied within 70S initiation complexes ribosome.AUGU3[14C]CHRCl.fMet-tRNA(Metf) and binary complex ribosome.AUGU3[14C]CHRCl. Various ways of the 70S initiation complex formation resulted in differently labelled products. Proteins S5, S7, S9, L1, L16 were thus identified as cross-linked with AUGU3[14C]CHRCl within an initiation complex obtained in the presence of initiation factors IF-1, IF-2, IF-3, whereas only proteins S5 and S7 were cross-linked within the complex obtained with the sole factor IF-2. Proteins S1, S3, L1 and L33 were labelled within the initiation complex obtained nonenzymatically but only protein S1 within the binary complex. In all complexes formed with use of initiation factors labelling of IF-2 factor was invariably observed.     

Flavonoids from the pods of Millettia erythrocalyx

From the pods of Millettia erythrocalyx, 2'-hydroxy-3,4-dimethoxy-[2',3':4',3']-furanochalcone, 2',3-dihydroxy-4-methoxy-4'-gamma,gamma-dimethylallyloxychalcone, (-)-(2S)-6,3',4'-trimethoxy-[2',3':7,8]-furanoflavanone, 3',4'-methylenedioxy-[2',3':7,8]-furanoflavonol and 6,3'-dimethoxy-[2',3':7,8]-furanoflavone were isolated, along with six other known flavonoids. Their structures were elucidated through analysis of their spectroscopic data.     

Prenylflavonoids from Flourensia fiebrigii

Three compounds: (2S)-8-(3'-methylbut-2'-enyl)-7,3',4'-trihydroxyflavanone, (2S)-8-(3'-methyl-4'-hydroxy-but-2'-enyl)-7,3',4'-trihydroxyflavanone and (2S)-8-(3'-methyl-4'-hydroxy-but-2'-enyl)-5,3',4'-trihydroxy-7-methoxyflavanone, along with five previously known compounds, were isolated from the aerial parts of Flourensia fiebrigii. Their structures were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques.     

6-Oxocytidine a novel protonated C-base analogue for stable triple helix formation.

2'-O-Methyl-3'-O-phosphoramidite building blocks of 6-oxocytidine 6 and its 5-methyl derivative 7, respectively, were synthesized and incorporated via phosphoramidite chemistry in 15 mer oligodeoxynucleotides [d(T72T7), S2; d(T73T7), S3] to obtain potential Py.Pu.Py triplex forming homopyrimidine strands. UV thermal denaturation studies and CD spectroscopy of 1:1 mixtures of these oligomers and a 21 mer target duplex [d(C3A7GA7C3)-d(G3T7CT7G3), D1] with a complementary purine tract showed a nearly pH-independent (6.0-8.0) triple helix formation with melting temperatures of 21-19 degrees C and 18.5-17.5 degrees C, respectively (buffer system: 50 mM sodium cacodylate, 100 mM NaCl, 20 mM MgCl2). In contrast, with the corresponding 15mer deoxy-C-containing oligonucleotide [d(T(7)1T7), S1] triplex formation was observed only below pH 6.6. Specificity for the recognition of Watson-Crick GC-base pairs was observed by pairing the modified C-bases of the 15mers with all other possible Watson-Crick-base compositions in the target duplex [d(C3A7XA7C3)-d(G3T7YT7G3), X = A,C,T; Y = T,G,A, D2-4]. Additionally, the Watson-Crick-pairing of the modified oligomers S2 and S3 was studied.     

Microbial transformation of xanthohumol

Microbial transformation of xanthohumol using the culture broth of Pichia membranifaciens afforded three metabolites, (E)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":4',3']-2', 4-dihydroxy-6'-methoxychalcone, (2S)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":7,8]-4'-hydroxy-5-methoxyflavanone and (E)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":2',3']-4'-hydroxy-5-methoxychalcone.     

Inhibition by prostacyclin and carbacyclins of endothelin-induced DNA synthesis in cultured vascular smooth muscle cells

Effects of prostacyclin and carbacyclins on endothelin-induced DNA synthesis were investigated in vascular smooth muscle cells. DNA synthesis was estimated by [3H]thymidine incorporation. Five carbacyclins used in this report were 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo [3.3.0]oct-2-en-3-yl) pentanoic acid (TEI-7165), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo[3.3.0]oct-2-en-3- yl]pentanoate (TEI-9090), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1-nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)penta noic acid (TEI-9063), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1- nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)pentanoate (TEI-1324), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-4-hydroxy-4-methyl-1- octenyl]bicyclo[3.3.0]oct-2-en-3-yl] pentanoic acid (TEI-3356). Prostacyclin and the carbacyclins inhibited the endothelin-induced DNA synthesis within the nanomolar range. These results suggest that prostacyclin and carbacyclins are possibly effective in inhibiting the proliferation of vascular smooth muscle cells under some situations in vivo.