Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Safrole”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2000

Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole.

Anew series of antinociceptive compounds belonging to the N-acylarylhydrazone (NAH) class were synthesized from natural safrole (7). The most analgesic derivative represented by 10f, [(4'-N,N-dimethylaminobenzylidene-3-(3', 4'-methylenedioxyphenyl)propionylhydrazine], was more potent than dipyrone and indomethacin, used as standards. The NAH compounds described herein were structurally planned by molecular hybridization and classical bioisosterism strategies on previously reported analgesic NAH in order to identify the pharmacophoric contribution of the N-acylarylhydrazone moiety and investigate the structure-activity relationship (SAR) in these series.

Acetates↗
PubMed1998

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole.

Four new aryl-sulfonamide derivatives (3a, 4a, 5a-b), having methylenedioxy group attached to phenyl ring, were prepared from natural safrole and evaluated as anti-inflammatory agents. The N-methylsulfonamide 3a and corresponding retrosulfonamide derivative 5a were more active than standards indomethacin and nimesulide, at the same molar concentration, in carrageenan-induced pleurisy assay.

Animals↗
PubMed1983

The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.

A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.

Adenine↗
PubMed1976

The effects of benzopyrene and safrole on biphenyl 2-hydroxylase and other drug-metabolizing enzymes.

A study was made of the nature and specificity of the increase in biphenyl 2-hydroxylase activity after preincubation of liver microsomal preparations with various carcinogens in vitro. This enhancement of enzyme activity in vitro was investigated in mouse, hamster and rat, and although the rat appears to be atypical in the variation of the pattern of 2- and 4-hydroxylation with age, similar enhancements were detectable in each species examined. An increase in biphenyl 2-hydroxylase activity was apparent 2h after intraperitoneal administration of safrole or benzopyrene to mature Wistar albino rats and appeared to be similar in nature to that observed after preincubation of liver microsomal preparations with the same chemical in vitro. Investigation of other drug-metabolizing enzyme systems suggests that the enhancing effects of carcinogens in vitro are specific for biphenyl 2-hydroxylase. No correlation between the enhancement of biphenyl 2-hydroxylase and inhibtion of biphenyl 4-hydroxylase was apparent.

Acetone↗
PubMed1988

Activating mutations in human c-Ha-ras-1 gene induced by reactive derivatives of safrole and the glutamic pyrolysis product, Glu-P-3.

Foci of transformed NIH3T3 cells were observed after transfection of plasmids containing the c-Ha-ras-1 protooncogene modified in vitro either with the 3-N,N-acetoxyacetyl derivative (N-AcO-AGlu-P-3) of the mutagenic L-glutamic acid pyrolysis product 3-amino-4,6-dimethyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-3) or with 1'-acetoxysafrole (AcO-S), a reactive derivative of the carcinogen safrole. DNA isolated from these foci were used in a second round of transfection, and the DNA obtained from the secondary transformants was analysed to determine the nature of mutations responsible for activating the protooncogene. The polymerase chain reaction method was used to amplify sequences of the gene likely to contain activating mutations, and these regions were then subjected to selective hybridization with specific oligonucleotides to locate and identify the point mutations. Five out of six transformants induced by N-AcO-AGlu-P-3 contained mutations at codon 61. Three of the codon 61 mutations were at the first base and the other two were at the third base, all were GC----TA transversions. Two AcO-S-induced transformants contained a GC----TA transversion, in one case at the first base of codon 61, in the other at the first base of codon 12. Another AcO-S-induced transformant, and the sixth transformant induced by N-AcO-AGlu-P-3 were apparently not mutated in codon 12, 61 or 117. Both N-AcO-AGlu-P-3 and AcO-S react predominantly with guanine residues in DNA, and all the mutations identified here were at GC base pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Metabolism of safrole in the rat.

The urinary metabolites of safrole (4-allyl-1,2-methylenedioxybenzene) in the rat were identified using gas chromatographic - mass spectrometric methods. The amounts of the individual metabolites excreted were determined gas chromatographically. Metabolite excretion was 93% in 72 hrs and most of this material (86%) consisted of metabolites formed via demethylenation of the methylenedioxy moiety. The other metabolic routes observed were allylic hydroxylation and the epoxide-diol pathway.

Animals↗
PubMed1977

[Metabolic activation by adrenal tissue in rats of a liver carcinogen: safrole].

In vivo and in vitro metabolisms by the rat adrenal tissue of safrol, a natural hepatocarcinogen, were studied by gas chromatography-mass spectrometry and compared to the hepatic metabolism. In the adrenals the epoxide-diol pathway was found besides demethylase and hydroxylase activities, suggesting that the adrenal cortex may participate to the metabolic activation of a procarcinogen.

Adrenal Glands↗
PubMedDate not supplied

Hydrolysis of the 2',3'-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases.

2',3'-Allylic epoxide derivatives of allylbenzene and its analogs estragole, eugenol, and safrole were synthesized, and their enzymatic conversion to dihydrodiols by cytosolic and microsomal epoxide hydrolases was examined. All four epoxides were good substrates for both epoxide hydrolases, with Michaelis constants in the low micromolar range. Two putatively selective inhibitors of cytosolic and microsomal epoxide hydrolases, trichloropropylene oxide and nordihydroguaiaretic acid, were used to inhibit the hydrolysis of these allylic epoxides. Minimal selectivity toward either hydrolase was seen with either inhibitor, suggesting that the "selectivity" of these inhibitors is highly substrate-dependent. The susceptibilities of these epoxides to rapid hydrolysis by both epoxide hydrolases may explain their low genotoxic potencies in vivo.

Allylbenzene Derivatives↗
PubMed1989

Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.

The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin.

Analgesia↗
PubMed1987

Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J x C3H/HeJ F1 mice.

Further information on the structure-activity relationships among the synthetic and naturally occurring alkenylbenzene derivatives was obtained by examining their hepatocarcinogenicities for mice following administration of one or a few doses prior to weaning. Under these conditions preweanling male C3H/HeJ mice were more susceptible than male C57BL/6J mice or females of either strain to liver tumor induction by 1'-hydroxyestragole (1'-hydroxy-1-allyl-4-methoxybenzene) and 1'-hydroxysafrole (1'-hydroxy-1-allyl-3,4-methylenedioxybenzene). Male C57BL/6J X C3H/HeJ F1 mice given a single dose of 1'-hydroxyestragole at 12 days of age developed approximately twice as many hepatomas per liver as did those given the same dose per g of body weight at 1 day of age. The acetylenic compounds 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole were the most potent derivatives studied; they were 5- and 10-fold more potent (based on the average numbers of hepatomas per liver) than the corresponding allylic benzene derivatives. 1'-Acetoxyestragole and 1'-acetoxysafrole had activities similar to those of their respective 1'-hydroxy derivatives; estragole derivatives were consistently 2- to 3-fold more potent than the related safrole derivatives. 1'-Hydroxyelemicin (1'-hydroxy-1-allyl-3,4,5-trimethoxybenzene), its acetic acid ester 1'-oxoestragole, and 3'-bromo-trans-anethole (3'-bromo-1-trans-propenyl-4-methoxybenzene) each had very weak, but statistically significant, hepatocarcinogenic activity. The propenylic derivatives cis-anethole, trans-isosafrole, 1:1 cis,trans-isosafrole, 3'-hydroxy-trans-anethole, piperine, and trans-cinnamaldehyde showed no hepatocarcinogenic activity at the levels examined. In contrast, the propenylic derivatives cis- and trans-asarone (1-propenyl-2,4,5-trimethoxybenzene) were each active; the hepatocarcinogenicities of the asarones were not inhibited by prior administration of pentachlorophenol, a sulfotransferase inhibitor that abolished the hepatocarcinogenicity of estragole under the same conditions. Furthermore, precocene II (6,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran), a cyclic propenylic plant metabolite and asarone analogue, showed strong hepatocarcinogenic activity similar to that of 1'-hydroxy-2',3'-dehydroestragole and 1'-hydroxy-2',3'-dehydrosafrole; precocene I (the 7-methoxy analogue of precocene II) was less active than precocene II but more active than cis-asarone.

Age Factors↗
PubMed1981

Biology of hepatocellular neoplasia in the mouse. III. Electron microscopy of safrole-induced hepatocellular adenomas and hepatocellular carcinomas.

A systematic, ultrastructural analysis wsa performed on safrole-induced hepatocellular adenomas and hepatocellular carcinoma(s) (HPC) in BALB/c mice. Adenomas were heterogeneous in cell composition containing dark-staining basophilic cells, pale-staining acidophilic cells, clear cells, and lipid-laden cells. Darkly staining cells resembled fetal hepatocytes. They had large nuclei with irregular borders and limited diversity of organelles. Rough endoplasmic reticulum was prominent and seen as parallel cisternae in single or double tracts often in association with mitochondria. Pale-staining cells contained abundant smooth endoplasmic reticulum. Other organelles were often displaced to the perinuclear or peripheral region of the cell. The clear cells resembled dark-staining or pale-staining cells but also containing large areas of glycogen deposition. Lipid-laden cells contained numerous, multisized lipid droplets in the cytoplasm. HPC contained cell types similar to those of the adenoma. In addition, they contained many anaplastic cells. These resembled hepatocytes but contained several other alterations. The most striking was an apparent increase in the number of altered mitochondria. The cytoplasm was often fluid with enlarged mitochondria with dense or pale matrices. The cristae were few and had altered configurations. Also, an apparent increase was seen in the number of microbodies. These were often clustered in one region of the cytoplasm. An increase in microbodies was also noted in other cell types of hepatocellular carcinomas. The results of this study demonstrated similarities in the cell types of the adenomas and HPC. This study also demonstrated differences, with the anaplastic cell being common only to the carcinoma. Due to the similarity of cell types, the adenoma should be considered a possible site of HPC development.

Adenoma↗
PubMed2006

Synthesis by-products from the Wacker oxidation of safrole in methanol using rho-benzoquinone and palladium chloride.

This paper reports the identification of a number of by-products, which are produced during the Wacker oxidation of safrole to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using rho-benzoquinone and palladium chloride when methanol is utilised as the solvent. Also described is the retrieval of these compounds from illicit samples from a clandestine laboratory, which was uncovered in South Australia in September 2003.

Journal Article↗