Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HEXESTROL”

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 145 records · Page 8Linked to original sources
PubMed1987

Steroid modulation of liver regeneration and hepatic microsomal enzymes in rats of either sex.

Rats of either sex as intact or partially hepatectomized (two-thirds liver removal) were injected s.c. daily for 7 days post-operatively with natural and synthetic estrogens, androgens or anabolic steroids, progesterone and adrenal cortical hormones and killed on day 10 at which time the livers were processed for microsomal analyses (protein, cytochrome P-450 and enzymes, aminopyrine demethylase and aromatic hydrocarbon or benzo[a]pyrene hydroxylase). Groups were also induced with phenobarbital injected i.p. on the last 3 days at 80 mg/kg each. With the intact males, hexestrol was the only estrogen which caused liver enlargement and at a daily dosage of 1.0 micrograms per rat as well as a decrease in the hydroxylase level. Estradiol benzoate (15 micrograms/rat daily) depressed cytochrome P-450 and the other steroids screened had little effect on the microsomal parameters except for a rise in demethylase with deoxycorticosterone acetate (1.0 mg). A greater sensitivity to estrogens and the other steroid types was noted with the partially hepatectomized males and in the direction of depressions in the microsomal elements, the respective data being expressed as percentages of the controls. Estrogens were better tolerated by the intact female and in general, liver enlargement was remarkable. Microsomal activity was elevated with estradiol benzoate or little affected by estrogens except for depressions in hydroxylase levels with equilin (15 micrograms) and the high dosages of hexestrol and diethylstilbestrol, the last agent also eliciting an increase in cytochrome P-450. No statistically significant effect on the microsomal parameters was observed with the intact female treated with 17-methyltestosterone and the anabolic steroids but decreases occurred on injection with testosterone propionate and the cortical hormones. As with the operated male, partially hepatectomized females exhibited no hepatotrophic response to estrogens and the microsomal changes were moderate with such agents as with the other steroid types and resembling the findings for intact males. Competitive inhibition was followed by Lineweaver-Burke analyses of aminopyrine demethylase in operated females treated with several of the steroids.

Animals↗
PubMed1987

[Clinical studies on 179 cases of prostatic cancer].

Between 1971 and 1984, 179 patients with prostatic cancer were admitted to our Hospital. These cases were studied retrospectively. The greatest number of patients were in their seventies. The patients ranged from 55 to 90 years old with an average age of 72.4 years. The most common symptoms were dysuria, urinary retention, pollakisuria and macrohematuria. About 76% of the chief complaints were related to urinary tract obstruction. There were 64 (35.8%), 21 (11.7%), 38 (21.2%) and 56 (31.3%) cases of stage A, B, C and D, respectively. Prostatic cancer was confirmed histopathologically at transurethral resection in 146 patients, transrectal needle biopsy in 25 patients, open prostatectomy in 3 patients, autopsy in 4 patients, and cryosurgery in 1 patient. The 1-, 3-, and 5-year actual survival rates of 162 cases were 89, 70 and 55%, respectively. The 5-year actual survival rate of stage A, B, C, and D was 72, 67, 55 and 34%, respectively. The 5-year actual survival rate for the cases treated with and without anti-androgen therapy was 72% and 73% for stage A, 66% and 75% for stage B, 58% and 44% for stage C and 37% and 12% for stage D, respectively. The cases treated with anti-androgen therapy was divided into the low dose (diethylstilbestrol less than 300 mg/day or hexestrol less than 30 mg/day) and high dose (diethylstilbestrol greater than or equal to 300 mg/day or hexestrol greater than or equal to 30 mg/day) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney.

Both synthetic and natural estrogens have been studied for their ability to induce renal carcinomas in castrated male hamsters after 9.0 months of treatment. Tumor foci were detected in frozen serial sections stained histochemically for estrase activity. Both diethylstilbestrol (DES) and 17 beta-estradiol had equal ability (100%) to induce renal tumors [approximately 20.5 +/- 3 (S.E.) tumor foci] in these animals. Hexestrol induced the same incidence and number of renal carcinoma foci as DES or 17 beta-estradiol. However, alpha -dienestrol and DES 3,4-oxide showed an 86 to 88% incidence of renal tumors in hamsters (approximately 10.8 +/- 3). When equilin and d-equilenin, components of therapeutic conjugated estrogens, were tested, only equilin had a 76% incidence of renal tumor foci (5.5 +/- 0.9). The ability of these stilbene and steroidal estrogens to compete for renal tumor estrogen receptor generally correlated well with their ability to cause renal tumorigenesis in the hamster with one notable exception. Although ethinyl estradiol competed as well as did DES or 17 beta-estradiol for estrogen receptor, had similar ability to induce renal progesterone receptor, and led to similar high serum prolactin levels as either DES or 17 beta-estradiol, it had only weak carcinogenic activity (21%) in the hamster kidney (0.6 +/- 0.5 foci). These data represent the first detailed analysis of the relative carcinogenic activity of different estrogens within a given tumor-inducing system, and based on the carcinogenicity data of hexestrol and alpha-dienestrol presented herein, they suggest that epoxidation of the olefinic double bond and the p-quinone metabolite of DES probably are not involved significantly in its carcinogenic activity. Moreover, the poor carcinogenic activity of ethinyl estradiol in this system, despite strong estrogenicity, suggests that estronic activity alone may not be sufficient to effect renal tumorigenesis in the hamster.

Adenocarcinoma↗
PubMed1978

The mass spectra of diethylstilbestrol and related compounds.

The low resolution mass spectra of E-3,4-bis-(p-hydroxyphenyl)-hex-3-ene (diethylstilbestrol), E-[1,1,1-3H3]3,4-bis-(p-hydroxyphenyl)-hex-3-ene, E-2,3-bis-(p-hydroxyphenyl)-but-2-ene (dimethylstilbestrol), E,E-3,4-bis-(p-hydroxyphenyl)hexa-2,4-diene (dienestrol) and 3,4-bis-(p-hydroxyphenyl)-hexane (hexestrol) were examined as the parent compounds, their diacetates, dimethyl ethers, and bis-trimethylsilyl ethers. In addition, the mass spectra of the diethyl ether and the hexadeuteriodimethyl ether of E-3,4-bis-(p-hydroxyphenyl)-hex-3-ene were studied. Each compound gives rise to several sets of characteristic fragment ions associated with loss of alkyl groups, loss of aryl groups and rearrangements. An ion of m/e 165 (C13H9) was found in the spectra of all the compounds studied. With the aid of high resolution mass spectrometry empirical formulae were assigned to major ions of the free diphenols.

Adenocarcinoma↗
PubMed2005

On-line coupling of pressurized capillary electrochromatography with end-column amperometric detection for analysis of estrogens.

An improved technique, pressurized capillary electrochromatography (pCEC) coupling with end-column amperometric detection (AD), was developed and used for the separation and determination of estrogens. The effects of pH value, composition of mobile phase, concentration of the surfactant sodium dodecyl sulfate (SDS) and applied voltage on separation were investigated. The electrochemical oxidation of diethylstilbestrol (DES), dienestrol (DE), and hexestrol (HEX) could be reliably monitored with a carbon electrode at 0.9 V (vs. Ag/AgCl). The pCEC analyses were performed on a capillary separation column packed with 3 microm C18 particles with an acetonitrile/water (31%: 69%) mobile phase containing Tris buffer (5 mmol/L, pH 4.5) and 4 mmol/L SDS. High voltage up to 12 kV reduced the retention time dramatically and still provided a baseline resolution. In addition, supplementary pressure prevented bubble formation and provided reliability and reproducibility of the pCEC performance. The detection limits for the three estrogens ranged from 1.2 to 2.2x10(-7) mol/L, about 10 20-fold lower than those obtained with pCEC-UV detection. To evaluate the feasibility and reliability of this system, the proposed pCEC-AD method was further demonstrated with fish muscle samples spiked with estrogens.

Acetonitriles↗
PubMed1982

3,4-bis(3'-hydroxyphenyl)hexane--a new mammary tumor-inhibiting compound.

The syntheses of the hexestrol derivatives 3,4-bis-(3'-hydroxyphenyl)hexane (4a), 3,4-bis(4'-fluoro-3'-hydroxyphenyl)hexane (4b), 3,4-bis(3',4'dihydroxyphenyl)hexane (4c), and 3,4-bis(3',4'-diacetoxyphenyl)hexane (4d) are described. All compounds showed a marked, competitive inhibition of the estradiol receptor interaction (Ka4c greater than Ka4a greater than Ka4d greater than Ka4b). Evaluated in the mouse uterine weight test compounds 4c and 4d almost reached the estrone effect, whereas 4a and 4b did not produce full uterotrophic response. Compounds 4a--d antagonized the estrone stimulated uterine growth of the immature mouse. Compound 4a (NSC-297170) exhibited a specific, dose-related growth inhibition of the estrogen responsive MCF-7 human breast tumor cell line. Tested on the 9,10-dimethyl-1,2-benzanthracene-induced hormone-dependent mammary adenocarcinoma of the Sprague-Dawley rat all compounds showed marked inhibition of tumor growth. As in all experiments compounds 4a and 4b, which is resistant to hydroxylation in 4'-position exhibited an identical pattern of action, which is different from that shown by compound 4c, the effect of compound 4a cannot be explained by its possible catechol metabolite 4c.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen treatment on androgen-dependent organs of male rats.

The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are described in the present paper. It has been shown that each preparation, administered separately for 10 days, induced a moderate decrease in the weight of the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha-reductase activity was also decreased; the epithelium secretory activity of the VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw) the following castration-like effects were observed: an abrupt fall in the weight of the accessory sexual glands, a decrease of DNA level and cell number in the VP as well as a suppression of the production of 5 alpha-reductase metabolites in this structure. Histologically, a marked degenerative changes in the VP secretory epithelium was observed; on the contrary an hyperplasia of connective and smooth muscle cells was evident. When FI alone was administered to rat, the above-mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and testosterone (T) levels, also an increase of testicular delta 5-3 beta-hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was administered alone or in combination with FI, bio-LH and T levels and enzyme activity decreased. We conclude that Hex administration in low doses, in combination with FI, could be an alternative method for a complete androgen blockade of the accessory sexual glands.

Androgen Antagonists↗
PubMed1994

Oxohexestrol derivatives labeled with fluorine-18. Synthesis, receptor binding and in vivo distribution of two non-steroidal estrogens as potential breast tumor imaging agents.

We have prepared two non-steroidal estrogens in the 2-oxohexestrol series labeled with the positron-emitting radionuclide fluorine-18, 1-fluoro-5-oxohexestrol (4) and 1-fluoro-2-oxohexesterol (5). We anticipated that the polar ketone function at the interior of these ligands would reduce their level of non-specific binding, which might increase the selectivity of their uptake in vivo. The two compounds were prepared by total synthesis: compound 4 was prepared in fluorine-18 labeled form by [18F]fluorine ion displacement on a suitably protected methanesulfonate precursor followed by deprotection under acidic hydrogenolytic conditions; the isomer 5 was prepared from a protected alpha-keto trifluoromethanesulfonate precursor with deprotection under basic conditions as the final step. The binding affinity of these hexestrol derivatives for the estrogen receptor was determined by competitive radiometric binding assays at 0 and 25 degrees C, and their lipophilicity (as octanol-water partition coefficients, log P values) and non-specific binding were estimated. The log P values determined by a reversed phase HPLC method were higher, relative to estradiol, than those calculated by the fragment method of Rekker. In tissue distribution studies in immature (50 g) rats, both of these compounds showed selective uptake in estrogen target tissues. At 1 h, activity in the uterus reached the level of 2.5-3.0% of the injected dose per gram tissue, with uterus-to-blood and uterus-to-muscle ratios of 14-20 and 8-14, respectively. The uptake efficiency and selectivity of these fluoro-oxohexestrols in principal estrogen target tissues is less than that of fluorine-18 labeled steroidal estrogens we have prepared previously, but their receptor-mediated uptake in certain secondary target tissues is substantial. The specific and non-specific components of target tissue uptake of these two compounds appear to be directly related to their non-specific binding and their binding selectivity.

Animals↗
PubMed1986

Influence of alkyl chain ramification on estradiol receptor binding affinity and intrinsic activity of 1,2-dialkylated 1,2-bis(4- or 3-hydroxyphenyl)ethane estrogens and antiestrogens.

The influence of a symmetrical introduction of CH3 substituents in the alpha or beta positions of the 1,2-dialkyl-1,2-bis(4-hydroxyphenyl)ethane estrogens hexestrol (ethyl, HES) and octestrol (n-propyl, OCES) [isopropyl (1), tert-butyl (2), sec-butyl (3), isobutyl (4)] and the 1,2-dialkyl-1,2-bis(3-hydroxyphenyl)ethane antiestrogens metahexestrol (ethyl, MetaHES) and metaoctestrol (n-propyl, MetaOCES) [isopropyl (5), tert-butyl (6), sec-butyl (7), isobutyl (8)] on estradiol receptor (E2R) binding affinity and intrinsic activity is described. The synthesis of compounds 1-8 was accomplished by reductive coupling of (a) the corresponding alpha-alkylbenzyl alcohols with TiCl3/LiAlH4 and separation of the meso diastereoisomers (compounds 2-4, 7, and 8), (b) alpha-tert-butyl-3-methoxybenzyl chloride with CoCl2/EtMgCl and isolation of the meso configurated isomer (6), and (c) the isopropyl phenyl ketones with TiCl4/Zn and subsequent hydrogenation of the corresponding cis-hex-3-enes (compounds 1 and 5). The binding affinity of 1-8 to the calf uterine E2R was measured relative to that of [3H]E2 by a competitive binding assay. Compounds 1 and 5 showed relative binding affinity (RBA) values exceeding those of HES and MetaHES, respectively. All other derivatives showed RBA values smaller than the corresponding parent compounds. The intrinsic activity was monitored in terms of uterotrophic and antiuterotrophic activity. It is striking that the introduction of a CH3 group in the alpha positions of MetaHES and MetaOCES led to compounds with full intrinsic activity (5-7), i.e., estrogens without antiestrogenic properties. No correlation between E2R binding affinity and intrinsic activity was found.

Animals↗
PubMed1978

An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone.

In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary.

Animals↗
PubMed1996

Determination of synthetic estrogens in illegal veterinary formulations by HPTLC and HPLC.

To determine the actual amount of diethylstilbestrol, hexestrol, and dienestrol in formulations such as pellets and oily injections that are illegally available on the Brazilian market, a simple methanol extraction is used for the analysis of the pellets and an ether extraction with Sephadex columns (for clean-up) is used for the oily injections. High-performance thin-layer chromatography is used for identification (as a qualitative and semiquantitative method), and high-performance liquid chromatography is used for quantitation. The results of the analysis show that all the formulations are not in accordance with the information listed on their labels.

Animals↗
PubMed1984

High incidence of hepatocellular carcinomas after synthetic estrogen administration in Syrian golden hamsters fed alpha-naphthoflavone: a new tumor model.

P8 80-100% incidence of multinodular hepatocellular carcinomas was observed in castrated male hamsters following synthetic estrogen treatment in the presence of 0.2-0.4% alpha-naphthoflavone (ANF) in the diet after 8.5-10 months. Induction of these liver tumors was detected as early as 3.5-4.0 months in low frequency. Of the synthetic estrogens studied, ethynylestradiol (CAS: 57-63-6) was a more potent inducer of these hepatic carcinomas than either diethylstilbestrol (CAS: 56-53-1) or hexestrol (CAS: 84-16-2). ANF, considered an inhibitor of P450-dependent multisubstrate monooxygenases, did not produce any liver tumors when administered alone for up to 12 months. Neither concomitant androgen nor progesterone (CAS: 57-83-0) treatment resulted in any hepatic carcinomas in animals maintained on ANF. Moreover, beta-naphthoflavone (CAS: 6051-87-2) treatment alone or in combination with these synthetic estrogens also resulted in no hepatic tumors. This new estrogen-induced liver tumor model could be useful to elucidate the casual relationship that exists between estrogenic hormones and hepatic tumors in humans.

Animals↗
PubMed1989

3(20)alpha-hydroxysteroid dehydrogenase activity of monkey liver indanol dehydrogenase.

Homogeneous indanol dehydrogenase from monkey liver catalyzed the reversible conversion of 3 alpha- or 20 alpha-hydroxy groups of several bile acids and 5 beta-pregnanes to the corresponding 3- or 20-ketosteroids. The kcat values for the steroids determined at pH 7.4 were low, but the kcat/Km values for the 3-ketosteroids were comparable to or exceeded those for 1-indanol and xenobiotic carbonyl substrates. The enzyme transferred the 4-pro-R-hydrogen atom of NADPH to the 3 beta- or 20 beta-face of the ketosteroid substrate. Competitive inhibition of the hydroxysteroid dehydrogenase activity of the enzyme by medroxyprogesterone acetate, hexestrol, and 1,10-phenanthroline suggests that both 1-indanol and hydroxysteroid are oxidized at the same active site on the enzyme. The specific inhibitor of the enzyme, 1,10-phenanthroline, suppressed the 3 alpha-hydroxysteroid dehydrogenase activity in the crude extract of monkey liver by 50%. The results strongly suggest that indanol dehydrogenase acts as a 3(20)alpha-hydroxysteroid dehydrogenase in the metabolism of certain steroid hormones and bile acids.

20-Hydroxysteroid Dehydrogenases↗
PubMed1996

Lysosomal storage of sulphated glycosaminoglycans induced by dicationic amphiphilic drug molecules: significance of the central planar ring system.

The immunomodulatory drug tilorone (2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one) and several congeners are known to disturb the lysosomal degradation of sulphated glycosaminoglycans and thereby induce lysosomal storage of glycosaminoglycans in cultured cells and intact organisms. The molecules of tilorone and congeners consist of a planar aromatic ring system symmetrically substituted with two aliphatic side chains each carrying a protonizable nitrogen. In a previous study it was proposed that non-degradable glycosaminoglycan-drug complexes are formed by electrostatic interactions and that additionally intermolecular interactions between the drug molecules due to electronic coupling of their central planar ring system are important for formation and stabilization of the glycosaminoglycan-drug complexes and thus for the drug side effect in question. The significance of the central planar ring system was tested in the present study by comparing tilorone and the compound bis(beta-diethylamino-ethylether)hexestrol (DH) with respect to their potencies to cause lysosomal glycosaminoglycan storage in cultured bovine corneal fibroblasts. DH has the same side chains as tilorone, but its central apolar moiety lacks planarity. At a concentration (1.75 muM) which did not cause enhanced secretion of the lysosomal enzyme beta-hexosaminidase (E.C. 3.2.1.52), DH was significantly less potent than tilorone in causing storage of [35S]glycosaminoglycans. This is taken as support of the hypothesis that the planar tricyclic ring system is essential for the high potency of tilorone and its congeners to exert this adverse action.

Adjuvants, Immunologic↗
PubMed1995

Molecular characterization by mass spectrometry of the human estrogen receptor ligand-binding domain expressed in Escherichia coli.

The ligand binding domain of the human estrogen receptor (hER-LBD), encompassing the sequence MDPS282AG...V595, has been expressed at high levels in Escherichia coli from a pET-23d vector, and a purified preparation has been characterized both by mass spectrometry and biochemical methods. Inclusion bodies from the bacterial expression were solubilized by sonication and the hER-LBD was purified to near homogeneity by affinity chromatography over an estradiol-Sepharose column in urea-containing buffer. This material ran as a single peak on reversed-phase HPLC, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed a band with apparent molecular mass of 31-32 kilodaltons (kDa), somewhat smaller than that expected from the construct (35.6 kDa). Edman degradation revealed a single sequence of MDPSAGDMRA, consistent with an intact N terminus. Further characterization of this material using low resolution matrix-assisted laser desorption ionization mass spectrometry indicated an apparent single protein species of average mass 33,143 daltons (Da). Detailed molecular analysis by electrospray ionization mass spectrometry, however, revealed that this purified hER-LBD preparation was actually composed of a number of both modified and unmodified LBD protein fragments between 32,900-33,400 Da. The bulk of this 33-kDa protein mixture consisted of three LBD protein fragments with C termini at Ala571 (70%), Ala569 (23%), and Ser575 (4%), with only a trace amount (3%) of the full length expressed LBD (MDPS282...V595; 35, 602 Da). These four protein species also appear to be partially chemically modified by carbamylation. The functional integrity of this hER-LBD preparation was investigated by a ligand-exchange assay, which showed that the hER-LBD retained full estradiol-binding capacity; specific, covalent labeling was also observed using either the electrophilic affinity-labeling ligand tamoxifen aziridine (TAZ) or the photoaffinity-labeling ligand hexestrol diazirine. Thus, this expressed hER-LBD preparation, while appearing nominally pure by conventional biochemical techniques and having the expected ligand-binding capacity, was shown by sensitive high resolution electrospray ionization mass spectrometry techniques to be largely truncated 20-26 amino acids from the expected C terminus and to have a substantial level of covalent modification arising from the urea.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1989

The hypotensive effect and antifungal activity of 3,3'-dihydroxy-alpha,beta-diethyldiphenylethane.

3,3'-Dihydroxy-alpha,beta-diethyldiphenylethane (I), an isomer of hexestrol (II), was found to have a strong hypotensive effect on rats and antifungal activity against some pathogenic fungi. The hypotensive effect of I (-100.0 +/- 21.0 mmHg, 10 mg/kg, i.v.) was stronger than that of II (-40.0 +/- 2.60 mmHg, i.v.). Unlike II and other oxystilbene-related compounds already tested, I showed prolonged hypotensive action at the dose of 10 mg/kg, and the blood pressure was not restored to the original level within 20 min. I also showed antifungal activity against all fungi tested (minimal inhibitory concentration: 10-120 micrograms/ml). It should be emphasized that by shifting the phenolic hydroxyl group to m-position, the biological activities were greatly increased.

Animals↗
PubMed1990

Hypotensive effects on spontaneously hypertensive rats and antifungal activity on various species of Fusarium oxysporum of diethylstilbestrol-related compounds.

The diethylstilbestrol-related compounds 3,3'-dihydroxy-alpha, beta-diethyldiphenylethane (I), diethylstilbestrol (II) and hexestrol (III) showed hypotensive effects on spontaneously hypertensive rats (SHR) and antifungal activities against all Fusarium oxysporum sp. tested. As previously reported, I had strong hypotensive action on normotensive rats at the dose of 10 mg/kg, while II and III showed weak hypotensive effects on these rats at the same dose. In this work, all three compounds also had hypotensive actions on SHR at the same dose. I showed the strongest hypotensive effect (-80.0 +/- 5.0 mmHg, 10 mg/kg, i.v.) on both SHR and normotensive rats. The three compounds also had antifungal activities against five kinds of Fusarium oxysporum sp. tested. Especially, II strongly inhibited the growth of Fusarium oxysporum f. sp. raphani IFO-9972 (minimum inhibitory concentration (MIC): 1.0 micrograms/ml).

Animals↗
PubMed1993

Structure-activity relationship of 3,3'-dihydroxy-alpha,beta-diethyldiphenylethane and its related compounds.

3,3'-Dihydroxy-alpha,beta-diethyldiphenylethane (I), 3,3'-dihydroxy-alpha,beta-diethylstilbene (II), hexestrol (III) and diethylstilbestrol (IV) have already been reported to show hypotensive effects on rats and exhibit phytogrowth-inhibitory activities. We have proposed that two phenolic hydroxyl groups in these compounds are necessary for the biological activities, and a structure-activity relationship for I-related compounds was accomplished using molecular-mechanics (MM) calculations. As a result, the following three findings were obtained; 1) the minimized conformational energy obtained from MM calculations, which is a parameter expressing the molecular stability, showed a relatively high correlation with the biological activities, 2) as results of quantitative structure-activity relationship (QSAR) analyses, the combination of the distance between two phenolic hydroxyl oxygens led to the regression equations with high correlation values, and 3) the idealized molecular model of the most active compound (I) showed the highest stability and had a particular conformation which differed from the other compounds (II-IV).

Animals↗