PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Heterocyclic Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 73 records · Page 4Linked to original sources
PubMed1975

Liver regeneration as influenced by the structure of aromatic and heterocyclic compounds.

The effect of aromatic hydrocarbons and derivatives and heterocyclic agents administered s.c. daily for the first 7 days or as dietary supplements was ascertained on the extent of liver regeneration in partially hepatectomized male rats over a period of 10 days. The monoalkylbenzenes proved ineffective by injection except for ethylbenzene and possibly n-propylbenzene and the introduction of the double or triple bond in the side-chain as exemplified by styrene and phenylacetylene, led to little change over the respective controls. A number of noncarcinogenic hydrocarbons accelerated the regenerative process but much higher s.c. dosages were required as compared to the carcinogenic hydrocarbons. As tested by the dietary route, the optimum effect among the phenylmethanes was reached with diphenylmethane, toluene, tri- and tetraphenylmethanes and the Sn analog, tin tetraphenyl being inactive. With the diets, carcinogens as BP or DBA at 0.10% were without effect whereas acenaphthene or fluoranthene at this level accelerated the regeneration. Although diets supplemented with anthracene or octahydroanthracene led to little change in liver increment, 9,10-dihydroanthracene, anthraquinone and anthrone comprised liver stimulants, an activity which did not extend to phenanthraquinone. Aniline and triphenylamine did not alter the control increment but diphenylamine was active as was also the case with o- and m-terphenyls, the p-isomer being ineffective. Although naphthalene lacked activity by either route, 1- and 2-phenylnaphthalenes proved stimulatory by injection and 1- and 2-naphthylamines, by diet. Among other derivatives, phenyl sulfide and its sulfoxide and sulfone were quite stimulatory in addition to heterocyclic S compound as benzothiophene, phenothiazine, phenoxathiin and thianthrene but not thianaphthene at the dietary levels screened. Several series were conducted with intact rats under the above conditions; ethyl-benzene and phenathrene injected s.c. at high levels did not alter the control dry- or wet liver-body weight ratios. The findings are summarized in Table 4.

Alkanes↗
PubMed2004

[Advances in the development of antitubercular agents containing no heterocyclic compounds in the pharmacophore. Part 2. Other derivatives except carboxylic acids].

This paper is the 21st communication in the series of review papers on the development of antituberculotics and the 10th communication summarizing the papers on the development of antituberculotics in recent 15 years. The first seven communications were devoted to heterocyclic compounds, the eighth one to the compounds containing an alkylsulfanyl group in the pharmacophore. The present paper sums up information concerning the compounds not containing a heterocycle in the pharmacophore which are not derivatives of carboxylic acids either. This completes the series of communications recording the development of antituberculotics in the recent period. The communication records papers published since 1980 because it intends to link up with a review paper published in 1982 (Ceskoslov. Farm., 1982; 31, 353-360).

Antitubercular Agents↗
PubMed1986

Enhancement of epoxide hydrolase activity in hepatic microsomes of mice given heterocyclic compounds.

The effects of dietary administration of equimolar doses (5 mmol/kg body wt per day) of trimethylene oxide, trimethylene sulfide, coumaran, benzofuran, indole, and indole-3-carbinol on the activities of microsomal epoxide hydrolase and several other xenobiotic metabolizing enzymes were measured in the liver of female CD-1 mouse. Every compound, with the exception of indole, caused a significant increase (P less than 0.01) of the styrene oxide epoxide hydrolase activity over controls in hepatic microsomes. These results indicate that the enzyme activity is elevated in vivo by several heterocyclic compounds with strained bond angles to a nucleophilic hetero-atom. In addition, the ability of sulfur-containing trimethylene sulfide and nitrogen-containing indole-3-carbinol to elevate the enzyme activity indicates that the heterocyclic oxygen atom is not an absolute requirement for this effect. Data from the other xenobiotic metabolizing enzymes indicate that trimethylene oxide and trimethylene sulfide enhance the epoxide hydrolase activity rather specifically, while not affecting the activities of the other enzymes measured. While the oxygen-containing coumaran and benzofuran both increased the NADH: quinone reductase activity in hepatic cytosol, the nitrogen-containing indole and indole-3-carbinol did not. This indicated a specific requirement for the oxygen atom in elevating the quinone reductase activity, which was not the case for the elevation of microsomal epoxide hydrolase activity.

Animals↗
PubMed1996

Quinaldine 4-oxidase from Arthrobacter sp. Rü61a, a versatile procaryotic molybdenum-containing hydroxylase active towards N-containing heterocyclic compounds and aromatic aldehydes.

Quinaldine 4-oxidase from Arthrobacter sp. Rü61a, an inducible molybdenum-containing hydroxylase, was purified to homogeneity by an optimized five-step procedure. Molecular oxygen is proposed as physiological electron acceptor. Electrons are also transferred to artificial electron acceptors with E'o > -8 mV. The molybdo-iron/sulfur flavoprotein regiospecifically attacks its N-heterocyclic substrates: isoquinoline and phthalazine are hydroxylated adjacent to the N-heteroatom at Cl, whereas quinaldine, quinoline, cinnoline and quinazoline are hydroxylated at C4. Additionally, the aromatic aldehydes benzaldehyde, salicylaldehyde, vanillin and cinnamaldehyde are oxidized to the corresponding carboxylic acids, whereas short-chain aliphatic aldehydes are not. Quinaldine 4-oxidase is compared to the two molybdenum-containing hydroxylases quinoline 2-oxidoreductase from Pseudomonas putida 86 [Tshisuaka, B., Kappl, R., Hüttermann, J. & Lingens, F. (1993) Biochemistry 32, 12928-12934] and isoquinoline 1-oxidoreductase from Pseudomonas diminuta 7 [Lehmann, M., Tshisuaka, B., Fetzner, S., Röger, P. & Lingens, F. (1994) J. Biol. Chem. 269, 11254-11260] with respect to the substrates converted and the electron-acceptor specificities. These dehydrogenases hydroxylate their N-heterocyclic substrates exclusively adjacent to the heteroatom. Whereas the aldehydes tested are scarcely oxidized by quinoline 2-oxidoreductase, isoquinoline 1-oxidoreductase catalyzes the oxidation of the aromatic aldehydes, although being progressively inhibited. Neither quinoline 2-oxidoreductase nor isoquinoline 1-oxidoreductase transfer electrons to oxygen. Otherwise, the spectrum of electron acceptors used by quinoline 2-oxidoreductase and quinaldine 4-oxidase is identical. However, isoquinoline 1-oxidoreductase differs in its electron-acceptor specificity. Quinaldine 4-oxidase is unusual in its substrate and electron-acceptor specificity. This enzyme is able to function as oxidase or dehydrogenase, it oxidizes aldehydes, and it catalyzes the nucleophilic attack of N-containing heterocyclic compounds at two varying positions depending on the substrate.

Aldehydes↗
PubMed2005

Sensitive assay for laboratory evolution of hydroxylases toward aromatic and heterocyclic compounds.

Powerful directed evolution methods have been developed for tailoring proteins to our needs in industrial applications. Here, the authors report a medium-throughput assay system designed for screening mutant libraries of oxygenases capable of inserting a hydroxyl group into a C-H bond of aromatic or O-heterocyclic compounds and for exploring the substrate profile of oxygenases. The assay system is based on 4-aminoantipyrine (4-AAP), a colorimetric phenol detection reagent. By using 2 detection wavelengths (509 nm and 600 nm), the authors achieved a linear response from 50 to 800 microM phenol and standard deviations below 11% in 96-well plate assays. The monooxygenase P450 BM-3 and its F87A mutant were used as a model system for medium-throughput assay development, identification of novel substrates (e.g., phenoxytoluene, phenylallyether, and coumarone), and discovery of P450 BM-3 F87A mutants with 8-fold improvement in 3-phenoxytoluene hydroxylation activity. This activity increase was achieved by screening a saturation mutagenesis library of amino acid position Y51 using the 4-AAP protocol in the 96-well format.

Bacterial Proteins↗
PubMed1983

Induction of specific monooxygenases by isosteric heterocyclic compounds of benz[a]anthracene, benzo[c]phenanthrene and chrysene.

Benzo[c]phenanthrene and a series of heterocyclic compounds (benzo[b]naphtho(1,2-d)thiophene; benzo[b]naphtho(2,1-d)thiophene; benz[a]acridine and benz[c]acridine) were tested to their capacity of inducing monooxygenase activity in rat liver by means of recording the metabolite profile of benz[a]anthracene formed in rat liver microsomal incubations. Although all compounds tested were found to be weak monooxygenase inducers the pretreatment of rats with them resulted in significant changes of the microsomal metabolite profile of benz[a]anthracene. The thiophenes equally gave rise to oxidation at the 5,6- and the 8,9-positions, whereas the benzacridines being isosteric to benz[a]anthracene favoured the K-region oxidation (5,6-oxidation). A structure-dependent effect of monooxygenase inducers on the metabolite profile of benz[a]anthracene is discussed.

Animals↗
PubMed1999

The effect of neurotrophic pyrimidine heterocyclic compounds, MS-818 and MS-430, on the regeneration of injured peripheral nerves.

The effects of pyrimidine heterocyclic compounds (MS-818 and MS-430) on nerve regeneration were evaluated using the cut-and-suture model of the right sciatic nerve of Wistar rats. After surgery, 1 or 5 mg/kg/day of MS-818 or MS-430 was intraperitoneally administered for 21 days. Control rats received the same surgery, but were administered saline instead of a drug. Each week from week 2, evoked muscle action potentials were recorded on the calf muscle to compare the ratio of latency and amplitude between tbe experimental and non-treated side. The specimens were taken from the tibial nerve for light microscopic observation; and the diameter, density and % axon area of myelinated axons were evaluated. Tbe results of EMG and histology suggest that administration of MS-818 is more effective than that of MS-430 and that administration of 5 mg/kg/day has a higher promoting effect than that of 1 mg/kg/day for sprouting and elongation of the severed nerve. These new neurotrophic pyrimidine compounds may be a group of possible substances effective in facilitating nerve regeneration.

Journal Article↗
PubMed1999

[Advances in the development of new antitubercular agents from a group of 5-membered heterocyclic compounds containing one type of heteroatom].

Tuberculosis and other mycobacterial diseases are considered at present to be one of the prominent problems of health services. Since 1985, and in particular in the 1990s, a search for new structures of antimycobacterial drugs is one of the first and foremost fields of chemotherapeutic research. The present review paper surveys the studies carried out in the field of five-membered heterocyclic compounds containing one species of the heteroatom (furan, thiophene, pyrrol, diazoles, triazoles, tetrazoles, indol, carbazol, and other more complex cyclic compounds of nitrogen and sulfur) since 1984, making use of the journal Chemical Abstracts and original papers.

Antitubercular Agents↗
PubMed2003

Synthesis, characterization and in vitro anti-invasive activity screening of polyphenolic and heterocyclic compounds.

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

Antineoplastic Agents↗
PubMed2006

Tautomerism-dependent ring construction of N-heterocyclic compounds from the reactions of 1-alkynyl Fischer carbene complexes and substituted pyrazolinones.

Four types of N-heterocyclic ring systems were successfully constructed from the reactions of 1-alkynyl Fischer carbene complexes (OC)5M=C(OEt)C[triple bond]CPh (1) (M = Cr, W) and substituted pyrazolinones (2). Reactions of 1 with 3-methyl-2-pyrazolin-5-one (2a), 3-n-propyl-2-pyrazolin-5-one (2b), 3,4-dimethyl-2-pyrazolin-5-one (2c), 3,4-trimethylene-2-pyrazolin-5-one (2d), or 3,4-tetramethylene-2-pyrazolin-5-one (2e) generated three kinds of Fischer aminocarbene complexes (3-5), and reactions of 1 with phenyl-substituted pyrazolinones, i.e., 3-phenyl-2-pyrazolin-5-one (2f) and its tautomer 3-phenyl-3-pyrazolin-5-one (2g), gave Fischer alkoxycarbene complexes (6) as the major products and aminocarbene complexes of types 3-5 as the minor products. Multiple tautomerism of pyrazolinones is attributed to the versatile formation of N-heterocyclic Fischer carbene complexes. Oxidative demetalation of complexes 3-6 with pyridine N-oxide or m-chloroperoxybenzoic acid efficiently afforded organic carbonyl products, and thus, strongly fluorescent syn-mixed-bimanes were prepared. The present findings constitute an alternative new method to synthesize mixed bimanes and other novel N-heterocyclic compounds.

Journal Article↗
PubMed1999

[Advances in the development of new antitubercular agents from a group of 5-membered heterocyclic compounds containing various heteroatoms].

Tuberculosis and other antimycobacterial diseases are considered to be one of the most important problems of the health service at present. Since 1985, and in particular in the 1990s, a search for new structures of antimycobacterial substances has ranked among the prior fields of chemotherapeutic research. The present review paper links up with the previous communications, and surveys the studies carried out in the field of five-membered heterocyclic compounds containing more heteroatoms since 1984. The most frequently investigated field is thiazole derivatives but the most successful papers originated in the group of oxazoles, where effective antituberculotics for clinical use can be expected in the future. The present research is based on the journal Chemical Abstracts and original papers.

Antitubercular Agents↗
PubMed1979

Mutagenicity of 43 structurally related heterocyclic compounds and its relationship to their carcinogenicity.

43 heteropolycyclic compounds belonging to a homologous series were investigated for mutagenicity. The results are compared with carcinogenicity data obtained with the same batches of compounds under conditions identical for all of them. Mutagenicity was tested in the Ames test with Salmonella typhimurium strains TA1535, TA1537 and TA100 in the presence and absence of liver 10 000 g supernatant from rats treated with Aroclor 1254. Carcinogenicity was tested by injection of the compounds into subcutaneous tissue of XVIInc/Z mice. 18 test compounds showed carcinogenic activity, some strongly, others only weakly. Of these, 17 were detected as mutagens: one weak carcinogen did not revert the Salmonella strains. No quantitative correlation was observed between the extents of the mutagenic and the carcinogenic effects. Of the 25 substances that did not produce tumours, 13 showed mutagenicity (12 in the presence, 2 in the absence, of the liver homogenate). The mutagenic effects of these compounds were quantitatively similar to those of the compounds that produced tumours. The most sensitive strain of Salmonella typhimurium was TA100. It detected all 30 mutagens. TA98 was mutated by 25 compounds, TA1537 by 16 compounds. No mutagenic effects were seen with TA1535. Possible reasons for the high percentage of apparently "false positives" in the Ames test and the lack of a quantitative correlation between the potency of the mutagenic and carcinogenic effects are discussed. It is suggested that the complexity of the metabolism of these heterocyclic compounds may lead to critical differences in metabolism in mouse subcutaneous tissue in vivo and in liver homogenates from rats treated with Aroclor. Therefore the present study will be extended to life-long oral and intrahepatic carcinogenicity tests leading to a higher proportion of metabolism in the liver.

Carcinogens↗