Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INDOLES”

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 127 records · Page 7Linked to original sources
PubMed1988

New heterocyclic ring systems--V synthesis and pharmacological activity of 6H-1,3,4-thiadiazolo [3',2':1,2]-5-oxopyrimido [5,4-b] indole derivatives and of 1-phenyl-6H-1,2,4-triazolo [1',5':1,2]-5-oxopyrimido[5,4-b] indole.

As a part of a study on analgesic and antiinflammatory active condensed heterocyclic compounds containing the pyrimidinic ring, a number of 6H-1,3,4-thiadiazolo [3',2':1,2]-5-oxopyrimido [5,4-b]indole and 1-phenyl-6H-1,2,4-triazolo [1',5':1,2]-5-oxopyrimido [5,4-b] indole were synthesized and tested. The results of pharmacological assays are reported and discussed.

Animals↗
PubMed1985

Studies in spiro heterocycles. Part 4(1): Investigation of the reactions of fluorinated 3-aroylmethylene-indol-2-ones with hydrazine and phenylhydrazine and synthesis of spiro [indole-3,3'-pyrazol]-2-ones.

Reactions of various 3-aroylmethylene-indol-2-ones with hydrazine and phenylhydrazine under exactly similar conditions have been carried out. The reaction with phenylhydrazine has not been investigated earlier. It was found that although the reaction with hydrazine hydrate afforded a spiro derivative viz., spiro[3H-indole-3,3'-(3H)pyrazol]-2(1H)-one, that with phenylhydrazine yielded simply a hydrazone derivative. Representative spiro compounds have been screened for antifertility activity but none was found active at a dose of 10 mg/kg in adult female rats.

Animals↗
PubMed1995

Polyfunctional indole-3-carbinol derivatives: 1-(indol-3-yl)glycerols and related compounds, beta-hydroxytryptamines and ascorbigens. Chemistry and biological properties.

Earlier interaction of indole-3-carbinols with L-ascorbic acid and chemical and biological properties of formed 2-skatylderivatives of L-ascorbic acid (ascorbigens) were discussed. In this presentation the properties and stereochemistry of products of interaction of polyfunctional biologically important indole-3-carbinols (indoleglycerol analogs and beta-hydroxytryptamine derivatives) with L-ascorbic acid are investigated. Biological significance of this reaction is discussed.

Animals↗
PubMed1991

Inhibition of tryptophan hydroxylase by food-derived carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole.

Food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were found to inhibit the activity of tryptophan hydroxylase (TPH) prepared from serotonin-producing murine mastocytomas, P-815 cells. Inhibition of TPH by Trp-P-2 was found to be competitive with the substrate L-tryptophan and non-competitive with the cofactor (6R)-L-erythro-5,6,7, 8-tetrahydrobiopterin. The inhibition proved to be reversible; by dialyzing the sample incubated with Trp-P-2, the enzyme activity could be fully recovered. Among a series of heterocyclic amines examined, Trp-P-1, Trp-P-2 and some other heterocyclic amines inhibited TPH activity. Trp-P-2 and other heterocyclic amines were the newly discovered naturally occurring inhibitors of the indoleamine metabolism.

Animals↗
PubMed1996

Indole inhibitors of human nonpancreatic secretory phospholipase A2. 1. Indole-3-acetamides.

Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad screening program was carried out to identify chemical structures which could inhibit hnps-PLA2. One of the lead compounds generated by the screening program was 5-methoxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid (13a). We describe the syntheses, structure--activity relationships, and pharmacological activities of a series of indole-3-acetamides and related compounds derived from this lead. This SAR was undertaken with the aid of X-ray crystal structures of complexes between the inhibitors and hnps-PLA2 which were of great value in directing the SAR.

Animals↗
PubMed1996

Indole inhibitors of human nonpancreatic secretory phospholipase A2. 2. Indole-3-acetamides with additional functionality.

As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A2(hnps-PLA2) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.

Crystallography, X-Ray↗
PubMed2003

Syntheses of 2-substituted indoles and fused indoles by photostimulated reactions of o-iodoanilines with carbanions by the SRN1 mechanism.

2-Substituted indoles (5a,b and 7) and fused indoles (9a-c, 11a,b, and 12) have been obtained by the S(RN)1 mechanism from photostimulated reactions of o-iodoaniline (1) and 1-halo-2-naphthalen-2-ylamines (3a,b) with enolate ions of acyclic (acetophenone (6), 2- (4a) and 4-acetylpyridine (4b)) and cyclic ketones (1- (8a) and 2-indanone (10a), 1- (8b) and 2-tetralone (10b) and 1-benzosuberone (8c)) in DMSO and liquid ammonia as solvents. The carbanions derived from 4a,b, 8a, and 10b are novel nucleophiles that form new C-C bonds by the S(RN)1 mechanism.

Journal Article↗
PubMed1996

Regioselective Synthesis of Mixed Indole 2,3-Bis(sulfides). A Study of the Mechanism of the Second Sulfenylation of Indole.

Sulfenylation of indole using sulfenyl chlorides leads to the initial formation of a 3-indolyl sulfide, while excess reagent introduces a second sulfide at the 2-position of the ring. The mechanism of this second sulfenylation has not, to date, been rigorously elucidated. The development of the first, regioselective synthesis of mixed indole 2,3-bis(sulfides) has allowed the study of the sulfenylation of 3-indolyl sulfides using a different sulfenyl chloride. Our results afford evidence that the reaction proceeds via an intermediate 3,3-disulfenylated indolenine species, with subsequent migration of one of the sulfide groups to the 2-position.

Journal Article↗
PubMed2004

Unprecedented stereospecific synthesis of a novel tetracyclic ring system, a hybrid of tetrahydropyrrolo[2,3-b]indole and tetrahydroimidazo[1,2-a]indole, via a domino reaction upon a tryptophan-derived amino nitrile.

Compounds containing a novel tetracyclic ring system, a hybrid of tetrahydropyrrolo[2,3-b]indole and tetrahydroimidazo[1,2-a]indole, are synthesized via an acid-mediated stereospecific domino tautomerization of a tryptophan-derived alpha-amino nitrile. Characterization of these new compounds and preliminary studies on the reactivity of the tetracyclic heterocyclic system are reported. [reaction: see text]

Journal Article↗
PubMed2002

In vitro metabolism of two heterocyclic amines, 2-amino-9H-pyrido[2,3-b]indole (A(alpha)C) and 2-amino-3-methyl-9H-pyridol2,3-b]indole (MeA(alpha)C) in human and rat hepatic microsomes.

2-Amino-9H-pyrido[2,3-b]indole (A(alpha)C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA(alpha)C) are two mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. In this study, we have investigated the in vitro metabolism of tritium-labelled A(alpha)C and MeA(alpha)C in hepatic microsomes from human pools, rats induced with polychlorinated biphenyl (PCB) (Aroclor 1254) and control rats. The microsomes were incubated with A(alpha)C and MeAaC and the detoxified and activated metabolites of A(alpha)C and MeA(alpha)C were separated and characterised by HPLC-MS. A(alpha)C is metabolised to two major and three minor detoxified metabolites, while MeA(alpha)C is metabolised to three major and one minor detoxified metabolites. Some A(alpha)C and MeA(alpha)C are activated by oxidation to the reactive metabolites N2-OH-A(alpha)C and N2-OH-MeA(alpha)C, respectively. These reactive N2-OH-metabolites react partially in the incubation system with formation of protein adducts, dimers and the parent compound by reduction of the N2-OH-metabolites. The distribution between the detoxified and activated metabolites in the different types of hepatic microsomes showed same pattern for both A(alpha)C and MeA(alpha)C. In PCB-induced rat microsomes, the major part of the metabolites are detoxified, only a little amount is activated. In control rat microsomes there is a fifty-fifty distribution between detoxification and activation, while the major part of the metabolites from the human microsomes are activated and reacts to form dimers and protein adducts. These data show that, in human hepatic microsomes compared to rat hepatic microsomes, a major part of A(alpha)C and MeA(alpha)C are metabolically activated to the reactive N2-OH-A(alpha)C and N2-OH-MeA(alpha)C.

Animals↗
PubMed2005

Experimental measurement of the induced dipole moment of an isolated molecule in its ground and electronically excited states: indole and indole-H2O.

Reported here are measurements of the magnitude and orientation of the induced dipole moment that is produced when an indole molecule in its ground S(0) and electronically excited S(1) states is polarized by the attachment of a hydrogen bonded water molecule in the gas phase complex indole-H(2)O. For the complex, we find the permanent dipole moment values mu(IW)(S(0)) = 4.4 D and mu(IW)(S(1)) = 4.0 D, values that are substantially different from calculated values based on vector sums of the dipole moments of the component parts. From this result, we derive the induced dipole moment values mu(I) (*)(S(0)) = 0.7 D and mu(I) (*)(S(1)) = 0.5 D. The orientation of the induced moment also is significantly different in the two electronic states. These results are quantitatively reproduced by a purely electrostatic calculation based on ab initio values of multipole moments.

Journal Article↗
PubMed2002

Oral cyclophosphamide therapy for patients with residual or relapsed indolent-type lymphoma after initial treatment for aggressive lymphomas. A sub-group of patients with apparent transformed indolent lymphoma.

Lymph node or bone marrow biopsy from sixty-one patients affected by aggressive non-Hodgkin lymphomas (NHL) were retrospectively evaluated to assess the histology at relapse. Eighteen cases (29.5%) were proven to have relapsed or persistent low-grade lymphoma after conventional therapy. In 5/18 patients association of low and high-grade lymphoma was detectable at diagnosis by bone marrow biopsy. In the remaining 13/18 no evidence of follicular lymphoma was detected at diagnosis. The outcome of these patients was compared to that of 43 patients relapsed without change in histology and treated by a second line therapy. Of these 43 patients, 13 were not responders (NR), 10 achieved a partial remission (PR) and 18 complete remission (CR). Two were lost during follow-up. The 18 patients with residual/relapsed indolent subtype received oral cyclophosphamide (100 mg/day for 15 days every month for six months): 3 of them had NR, 5 CR, and 10 PR. The overall survival (OS) median time was 39 months in low-grade resistant/relapsed patients and 20 months in patients with aggressive histology. OS at 24 months was 71 and 41%, respectively, (p < 0.02). Most of the patients with high-grade disease were refractory or relapsed after a median of five months, whereas cases with low-grade NHL showed a long lasting stable PR. We suggest that the higher grade patients with residual or relapsed low grade lymphoma were, in fact, transformed low-grade at diagnosis and, after removing the more aggressive component by chemotherapy, it is possible to manage these patients by conventional therapy for indolent lymphomas.

Administration, Oral↗
PubMed1987

Tumor induction in mice administered neonatally with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole or 3-amino-1-methyl-5H-pyrido[4,3-b]indole.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), which is a potent mutagen from pyrolysates of tryptophan, was given subcutaneously to neonatal ICR mice, and all animals were observed for 1 year. Tumors of the livers and lymphoreticular tissue were induced. In the mice given Trp-P-1, the incidences of these tumors were as follows: liver tumors in 45% of the males; malignant lymphoma in 13% of the males and in 24% of the females. In the mice given Trp-P-2, the incidences of liver tumors in the males were dose-dependent (12.5 mg/kg, 12%; 25 mg/kg, 18%), while those of malignant lymphoma varied within a range from 5 to 19%. Statistical analysis revealed that the incidences of the liver tumor in the mice given Trp-P-1 or Trp-P-2 and those of lymphoma in the mice given Trp-P-1 were significantly higher than those of the controls. In the control mice, the incidences of tumors were as follows: malignant lymphoma in 5% of the females; lung tumor in 14% of both sexes.

Age Factors↗
PubMed2004

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-9H-pyrido[2,3-b]indole (AalphaC) and identification of DNA adducts in organs from rats dosed with MeAalphaC.

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation to the corresponding N2-OH derivatives. The proximate mutagenic N2-OH derivatives of MeAalphaC and AalphaC did not react with deoxynucleosides or DNA. However, upon acetylation with acetic anhydride both reacted with 2'-deoxyguannosine and 3'-phospho-2'-deoxyguanosine, resulting in one adduct each, but not with other nucleosides or nucleotides. The adducts were identified as N2-(2'-deoxyguanosin-8-yl)-MeAalphaC, N2-(2'-deoxyguanosin-8-yl)-AalphaC, N2-(3'-phospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3'-phospho-2'-deoxyguanosin-8-yl)-AalphaC by comparison with adducts of known structure obtained by reaction of the parent amines with acetylated guanine N3-oxide. N2-OH-MeAalphaC and N2-OH-AalphaC reacted with calf thymus DNA after addition of acetic anhydride. 32P-postlabelling analysis of modified DNA showed one major adduct co-migrating with N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-AalphaC, respectively. Some minor adducts presumed to be undigested oligomers were also detected. 32P-postlabelling analysis of DNA from several organs of rats dosed orally with MeAalphaC showed that in vivo N2-(2'-deoxyguanosin-8-yl)-MeAalphaC also was the major adduct formed. Relative adduct level in DNA isolated from the liver of the rats was about 50.40 adducts/10(9) nt. The adduct levels were approximately 4-fold lower in the colon and the heart and approximately 12-fold lower in the kidney of the rats.

Acetic Anhydrides↗
PubMed1986

Boron and ectomycorrhizal influences on indole-3-acetic acid levels and indole-3-acetic acid oxidase and peroxidase activities of Pinus echinata Mill. roots.

The level of indole-3-acetic acid (IAA) in shortleaf pine (Pinus echinata Mill.) roots was increased by inoculation with the ectomycorrhizal fungus Pisolithus tinctorius (Pers.) Coker and Couch. Indole-3-acetic acid oxidase activity was also increased suggesting that the increased level of IAA was the result of increased synthesis. Boron fertilization reduced IAA levels in roots inoculated with P. tinctorius but not in noninoculated roots.

Journal Article↗
PubMed1967

Studies on the oxidation of indole-3-acetic Acid by peroxidase enzymes. I. Colorimetric determination of indole-3-acetic Acid oxidation products.

The method described here is based on a brief report by Harley-Mason and Archer. It involves the use of p-dimethylaminocinnamaldehyde (DMACA), a vinylogue of Ehrlich's reagent, as a color reagent for indoles. Colorimetric analyses of indoleacetic acid (IAA) oxidation reaction mixtures were made with the DMACA reagent as a solution rather than a spray. DMACA reagent will yield a wine-red color with IAA oxidation products in solution. Under similar conditions DMACA reacts with authentic IAA to yield only slight coloration at best. In comparison with other indoles, DMACA is more relative with IAA oxidation reaction products than either Salkowski or Ehrlich's reagents. Data discussed support a concept that the color produced with DMACA is due to the presence of tautomeric oxidation product(s) of IAA.

Journal Article↗