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1.
A rationale based upon coenzyme Q10 (CoQ10, ubiquinone) for the synthesis of potential antitumor agents constitutes a new approach in the search toward chemotherapy of cancer. The antitumor activities of 38 alkyl-1,4-benzoquinones, analogs of coenzyme Q, 24 of which are new compounds, are described. The 10 best antitumor analogs of CoQ all showed long-term cures of Walker carcinosarcoma 256 in rats. Particularly impressive were the 6-n-octylmercapto-5-chloro-2,3-dimethoxy-1,4-benzoquinone (NSC 252188), which cured six out of six rats with , 6-phytyl-5-hydroxy-2,3-dimethoxy-1,4-benzoquinone (NSC 277818) (four out of four cures, ), and 5-phytyl-2,3-dimethoxy-1,4-benzoquinone (NSC 276371) (three out of six cures, ). In general, a 5-chloro or 5-hydroxy group on the quinone nucleus or a side chain with unsaturation and branching, such as the phytyl side chain of NSC 277818 and NSC 276371, seemed to increase antitumor activity. Although a perfect correlation was not to be expected, many of the most potent antitumor analogs were also among the best in vitro inhibitors of the mitochondrial CoQ10-enzymes, succinoxidase, and NAD oxidase. 相似文献
2.
Prostaglandin congeners wherein the 15-hydroxy group is moved to the C16, C17, or C20 position or is replaced by a hydroxymethyl group were prepared
the 1,4-addition of a lithium trialkyl-
-alkenyl alanate to an appropriate cyclopentenone. Several of the 16-hydroxy derivatives showed significant activity as constrictors of the isolated gerbil colon and in bronchodilator and anti-secretory assays. 相似文献
3.
M. Brawner Floyd Robert E. Schaub Martin J. Weiss 《Prostaglandins & other lipid mediators》1975,10(4):289-296
Prostaglandin congeners wherein the 15-hydroxy group is moved to the C16, C17, or C20 position or is replaced by a hydroxymethyl group were prepared via the 1,4-addition of a lithium trialkyl-trans-alkenyl alanate to an appropriate cyclopentenone. Several of the 16-hydroxy derivatives showed significant activity as constrictors of the isolated gerbil colon and in bronchodilator and anti-secretory assays. 相似文献
4.
Sun-Shine Yuan 《Steroids》1982,39(3):279-289
A-ring enollactones , or derived from 4-cholesten-3-one, testosterone benzoate or 3-oxo-4-estren-17β-yl benzoate were condensed with [1,2-13C2]acetyl chloride to give intermediates , or . and were cyclized by acid or base to give 3,4-13C2-labeled 4-cholesten-3-one and testosterone, respectively. [3,4-13C2]4-Cholesten-3-one was converted via reduction of its trimethylsilyl enol ether to [3,4-13C2]cholesterol. Acetyl enollactone was cyclized in acetic acid to [3,4-13C2]3-oxo-4-estren-17β-yl benzoate followed by aromatization and hydrolysis to produce [3,4-13C2]estradiol-17β. Alternatively, cyclization of with base afforded [3,4-13C2]3-oxo-4-estren-17β-ol directly, which was then oxidized and aromatized to yield [3,4-13C2]estrone. Ozonolysis of progesterone, conversion to the diketal ester and acylation followed by acid hydrolysis furnished [3,4-13C2]progesterone. 相似文献
5.
Elizabeth M.K. Leovey Niels H. Andersen Pamela Bissonette 《Prostaglandins & other lipid mediators》1979,17(1):19-37
, originally introduced as an inadvertent contaminant in solutions used for evaluating the stability of prostaglandins, proved to lead to the rapid disappearance of the cyclopentenone unit of PGA2 (as monitored by circular dichroic spectroscopy). The cyclopentenone unit is converted, in various metabolites, to a 9-keto, 9α or 9β-hydroxy group lacking the ring unsaturation. The major EtoAc-soluble 9-hydroxy metabolite (Compound-I) was shown to be 9α, 15α-dihydroxy-2,3,4,5-tetranor-13--prostenoic acid. Similar tetranor 9-hydroxy metabolites with one additional degree of unsaturation, and with a 9β-hydroxy group, also occur but these have not been fully characterized. Only two of the wide range of 9-keto metabolites are fully characterized by mass spectral (MS) data: 9,15-oxo-2,3,4,5-tetranorprostanoic acid and 9,15-oxo-2,3,4,5-tetranor-13--prostenoic acid. The water soluble metabolites have not been characterized further.The fully characterized metabolites together with MS data from mixtures of minor metabolites indicate that can perform the following transformations: β-oxidation, dehydrogenation at C-15, reduction of the enone carbon-carbon double bonds (both Δ10,11 and Δ13,14), reduction of the 9-ketone, and possibly migration of the cyclopentyl double bond (Δ10,11 → Δ11,12). metabolizes 15-epimeric PGA2 equally readily with the production of similar products. PGA1 affords less 9-keto metabolites with compound I constituting 33% of the product by HPLC analysis. displays some enantioselectivity, PGA2 and 15-epi-PGA2 are each metabolized more rapidly than their enantiomers. Other prostaglandins appear to be less readily metabolized. 相似文献
6.
Labeled n-alkanes administered to the grasshopper are hydroxylated at or near the middle of the carbon chain. The secondary alcohols formed are then esterified. Chain length specificity is evident in both the hydroxylation of n-alkanes and the esterification of secondary alcohols, with the shorter chain C23, C21, C19, and C25 compounds converted to secondary alcohol wax esters more readily than the longer chain C27, C29, and C31 compounds. Secondary alcohols and ketones are not reduced to alkanes. 相似文献
7.
Mary A. Napier Irving H. Goldberg Otto D. Hensens Ray S. Dewey Jerrold M. Liesch Georg Albers-Schönberg 《Biochemical and biophysical research communications》1981,100(4):1703-1712
On the basis of spectroscopic evidence, opening of a five-membered cyclic carbonate ring (1,3-dioxolan-2-one) in the C15-subunit of the previously determined partial structure (Fig. 1) of the major neocarzinostatin chromophore (NCS-Chrom ), is proposed to account for its base-catalyzed methanolysis to NCS-Chrom . NCS-Chrom , apparently an authentic natural product present as a minor component in all preparations of NCS studied, was found to be formally equivalent to the hydrolysis/decarboxylation product of the cyclic carbonate functionality in NCS-Chrom . The mercaptan-dependent DNA strand-scission activity, equivalent for NCS-Chrom , and , is independent of the integrity of the cyclic carbonate ring system and implicates a secondary site in the C15-substructure for mercaptan activation. 相似文献
8.
Oxygen inhibits CO2 fixation by mesophyll protoplast extracts of the C3 plants, and , but stimulates the pyruvate induced CO2 fixation by mesophyll protoplast extracts of the C4 plants and . The former is reversed by increased levels of bicarbonate, whereas the latter effect is independent of bicarbonate concentration. The results are consistent with the proposal that oxygen inhibits C3 photosynthesis by competing with CO2 in the RuDP carboxylase/oxygenase system. The oxygen enhancement of C4 mesophyll photosynthesis is proposed to be due to pseudocyclic electron flow supplying additional ATP for the CO2 fixation process. 相似文献
9.
The crystal and molecular structure of prostaglandin A1 (PGA1) has been determined by X-ray diffraction. (Space group P212121, , . Comparison of the structure of PGA1 with that of PGF1β (determined previously as the tribromobenzoate) indicates significant differences in the relative intramolecular side chain orientations. However, conformation and torsional angles within each side chain of PGA1 are retained with little or no change in comparison with PGF1β, indicating the presence of the C15-bromobenzoate groups in the latter have had little effect in altering internal side chain conformation in the solid state. The overall differences in relative side chain orientation in PGA1 are attributable to chemical and conformational changes in the substituted cyclopentane moiety (C8-C12). 相似文献
10.
Penile intromissions have been thought to be the primary stimulus for reflex ovulation in light-induced persistent estrus (LLPE) rats, even though other stimuli also trigger reflex ovulation. To clarify the nature of these noncoital stimuli, intact (nonadrenalectomized) LLPE rats were briefly exposed to a variety of environmental stimuli, other than intromissions, and checked for ova 19–22 hr later. Summary of results (number of rats ovulating/number of rats tested): (A1) home cage (); (B1) home cage + vaginal taping (); (C1) home cage + male-soiled bedding (); (D1) novel cage (); (E1) novel cage + vaginal taping (); (F1) novel cage + vaginal taping + male-soiled bedding (); (G1) novel cage + vaginal taping + male-soiled bedding + male mounts without intromissions (). The percentage of LLPE rats that ovulated in the last-mentioned test condition was related to the degree of proceptivity/receptivity of the LLPE females. Eight of eight proceptive LLPE females ovulated, but only nonproceptive females ovulated. To account for reflex ovulation in the absence of intromission it has been suggested that adrenal progesterone (P) stimulates release of an ovulatory quota of luteinizing hormone. This study demonstrates no significant differences in percentage of LLPE females ovulating in corresponding groups of adrenalectomized (ADX) and adrenal-intact females. Summary of results: A2 = , B2 = , C2 = , D2 = , E2 = , F2 = , G2 = . Conclusion: (a) Exposure to a factor in male-soiled bedding induces reflex ovulation in a significant proportion of adrenal-intact LLPE animals while exposure to a novel cage and/or vaginal taping does not, (b) penile intromissions are not the primary stimulus for reflex ovulation in intact proceptive LLPE rats, and (c) adrenal P is not required for reflex ovulation after tests with noncoital stimuli. 相似文献
11.
The factors that affect reliable estimations of mutation rates (μ) in cultured mammalian somatic cell populations by fluctuation analysis are studied experimentally and statistically. We analyze the differential effect of the final cell population size in each culture (Nt) and the number of parallel cultures (C) on the variation in the rate estimates () inferred from the P0 method. The analysis can be made after the derivation of the variance of , which is a measure of variation of for a given combination of Nt and C in a number of repeat experiments. The variance of is inversely proportional to C and to the square of Nt. Nt determines the probability of occurrence of mutation in a cell culture. By influencing the size of P0, Nt also determines whether a rate estimate is obtainable from the experiment. Since Po is estimated from the fraction of cultures containing no mutation in a set of C cultures, C becomes a determining factor for the accuracy of . The rate estimated from is biased, but the bias is in general 2 orders of magnitude smaller than . By the selection of an appropriate combination of Nt and C for the experiment, this bias can be reduced even further.Based on the notion of comparing two proportions, we propose a test statistic and have applied it to experimental results for a test of equality of mutation rates in different cell lines. This development places the comparison of mutation rates on a statistical basis. 相似文献
12.
Purification and crystallisation procedures are reported for azurin and cytochrome c′ from Alcaligenes denitrificans and Alcaligenes sp. NCIB 11015. The azurin crystals from A. denitrificans are suitable for high-resolution X-ray structure analysis. They are orthorhombic, space group C2221 (with marked tetragonal pseudo-symmetry), cell dimensions , with two molecules per asymmetric unit. The cytochrome c′ crystals from both species are hexagonal, space group P6122 (or P6522), cell dimensions , γ = 120 °, with one subunit (molecular weight 14,000) in the asymmetric unit. 相似文献
13.
Karl M. Beem Jane S. Richardson David C. Richardson 《Journal of molecular biology》1976,105(2):327-332
The Mn superoxide dismutase from Escherichia coli has been obtained in three crystal forms: (I) from 68% saturated (NH4)2SO4, space group P222 or P2221, , with one subunit per asymmetric unit; (II) from 50% polyethylene glycol 6000, space group C2221 (with approx. P41212 symmetry), , with four subunits (2 molecules) per asymmetric unit; (III) from 52% polyethylene glycol with a different method of preparing the enzyme solution, space group P21212, , with two subunits per asymmetric unit.The yeast mitochondrial Mn superoxide dismutase has yielded the same crystal form both from 30% 2-methyl-2,4-pentane diol and from 23% polyethylene glycol 6000: space group P212121, , with four subunits (one molecule) per asymmetric unit.A full X-ray crystallographic study of at least one of these enzymes is planned. 相似文献
14.
15.
Yoshio Yamamoto Kazuo Torii Nakamura Yoichi Iitaka Yukio Mitsui Kaoru Miyamoto Hisayuki Matsuo Kozo Narita Nobuo Yoshida 《Journal of molecular biology》1981,145(1):285-287
The crystals of ribonuclease St, the extracellular ribonuclease from Streptomyces erythreus, have been obtained from (NH4)2SO4 solution with acetate buffer (pH 4.1). The crystals belong to a monoclinic space group C2 with dimensions . There are two protein molecules per asymmetric unit. The crystals diffract beyond 2.0 Å resolution. 相似文献
16.
Soybean agglutinin crystallizes in the monoclinic space group C2 with unit cell dimensions and one tetramer of 120,000 Mr per asymmetric unit. The crystals are suitable for high-resolution work. 相似文献
17.
Christine De Paillerets Jacques Gallay Michel Vincent Monique Rogard Annette Alfsen 《生物化学与生物物理学报:生物膜》1981,644(1):134-142
The lipid dynamics of the adrenocortical microsomal membranes was studied by monitoring the fluorescence anisotropy and excited state lifetime of a set of anthroyloxy fatty acid probes (2-, 7-, 9- and 12-(9-anthroyloxy)-stearic acid (AP) and 16-(9-anthroyloxy)palmitic acid (AS). It was found that a decreasing polarity gradient from the aqueous membrane interface to the membrane interior, was present. This gradient was not modified by the proteins, as evidenced by comparison of complete membranes and derived liposomes, suggesting that the anthroyloxy probes were not in close contact with the proteins. An important change of the value of the mean rotational relaxation time as a function of the position of the anthroyl ring along the acyl chain was evidenced. In the complete membranes, a relatively more fluid medium was evidenced in the C16 as compared to the C2 region, while the rotational motion appeared to be the most hindered at the C7–C9 level. In the derived liposomes, a similar trend was observed but the mobility was higher at all levels. The decrease of the mean rotational relaxation time was more important for 12-AS and 16-AP. Temperature dependence of the mean rotational relaxation time of 2-AS, 12-AS and 16-AP in the complete membranes revealed the existence of a lipid reorganization occurring around 27°C and concerning mainly the C16 region. The extent to which the acyl chain reacted to this perturbation at the C12 level depended on pH. The presence of proteins increased the apparent magnitude of this reorganization and also modified the critical temperature from approx. 23°C in the derived liposomes to approx. 27°C in the complete membranes. Thermal dependence of the maximum velocity of the , the second enzyme in the enzymatic sequence, responsible for the biosynthesis of the in the adrenal cortex microsomes, was studied. The activation energy of the catalyzed reaction was found to be low and constant () in the temperature range 16–40°C at pH 7.5, 8.5 and 9, corresponding to the minimum, intermediate and maximum rate, respectively. A drastic increase of the activation energy () was observed at temperature below 16°C at pH 7.5. A correlated change of the as function of temperature was detected; at 36°C while at 13°C the value shifted to 8.7. The pH range of the group ionization was narrower at 13°C. In contrast with the behaviour of the , the was apparently unaffected by the lipid reorganization at 27°C. It is suggested that this enzyme possesses a different and more fluid lipid environment than the bulk lipids. 相似文献
18.
Crystals of calotropin DI (Mr 23,400), have been prepared by microdialysis against 5% (w/v) polyethylene glycol 20,000 in water, pH 7.0. They have orthorhombic space group P212121 with cell parameters . Crystals of calotropin DII (Mr 24,000), prepared by the same technique against 5% (w/v) polyethylene glycol 20,000 in phosphate buffer of low ionic strength, pH 7.0, display monoclinic space group C2 with cell parameters . In both cases, there is only one molecule in the asymmetric unit. 相似文献
19.
Immunity protein, an inhibitor of the ribonuclease activity of the protein antibiotic colicin E3, crystallizes in the orthorhombic space group C222 with cell dimensions and one molecule of Mr 9800 per asymmetric unit. The crystals are suitable for high resolution X-ray analysis. 相似文献
20.
Utilization of C20-polyunsaturated fatty acids by a yeast fatty acid desaturase mutant 总被引:1,自引:0,他引:1
M A Williams D W Taylor J Tinoco M A Ojakian A D Keith 《Biochemical and biophysical research communications》1973,54(4):1560-1566
A study was made of the utilization of C20-polyunsaturated fatty acids by the fatty acid desaturase mutant , Arachidonic acid, 8,11,14-eicosatrienoic acid, and 5,8,11,14,17-eicosapentaenoic acid were about equally effective in supporting growth with lactate as the carbon source. The relative proportion of these fatty acids in total cell fatty acids was . 50%. 5,8,11-eicosatrienoic acid synthesized from oleate was less effective. Very little growth occurred with 11,14,17-eicosatrienoic acid or with 11,14-eicosadienoic acid. These results indicate the usefulness of the yeast mutant as a eucaryotic model for study of membrane systems enriched in specific C20-polyunsaturated fatty acids. 相似文献