Search results for "Cyclic compound"
showing 10 items of 819 documents
Structure Learning in Nested Effects Models
2007
Nested Effects Models (NEMs) are a class of graphical models introduced to analyze the results of gene perturbation screens. NEMs explore noisy subset relations between the high-dimensional outputs of phenotyping studies, e.g., the effects showing in gene expression profiles or as morphological features of the perturbed cell. In this paper we expand the statistical basis of NEMs in four directions. First, we derive a new formula for the likelihood function of a NEM, which generalizes previous results for binary data. Second, we prove model identifiability under mild assumptions. Third, we show that the new formulation of the likelihood allows efficiency in traversing model space. Fourth, we…
Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones
2020
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions. peerReviewed
Detoxication of carcinogenic fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1-1 variants and glutathione.
1998
AbstractEpidemiological studies suggest that individuals differing in the expression of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polycyclic aromatic hydrocarbons (PAH). This study reports the catalytic efficiencies (kcat/Km) of two naturally occurring variants, GSTP1-1/I-105 and GSTP1-1/V-105, towards a series of fjord-region diol epoxides representing potent biologically active PAH metabolites, and two GSTP1-1 mutants with Ala105 and Trp105 in the active site. The results indicate that individuals who are homozygous for the allele encoding GSTP1-1/V-105 might be more susceptible to PAH carcinogenesis due to…
11H‑Pyrido[3′,2′:4,5]pyrrolo[3,2‑c]cinnoline and Pyrido[3′,2′:4,5]pyrrolo[1,2‑c][1,2,3]benzotriazine: Two New Ring Systems with Antitumor Activity
2014
Derivatives of new ring systems 11H-pyrido[3',2':4,5]pyrrolo[3,2-c]cinnoline and pyrido[3',2':4,5]pyrrolo[1,2-c][1,2,3]benzotriazine have been prepared from the key intermediates 2-(1H-pyrrolo[2,3-b]pyridin-2-yl)anilines in excellent yields (94-99%) and screened by the National Cancer Institute (Bethesda, MD) on about 60 human tumor cell lines derived from nine cancer cell types. The tested compounds exhibited antiproliferative activity against all the human cell lines, showing comparable MG_MID (mean graph midpoint) values in the range of 0.74-1.15 μM. A particular efficacy was observed against the leukemia subpanel (GI50 = 0.73-0.0090 μM). Flow cytometric analysis of the cell cycle demons…
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…
2008
Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
Synthesis of new melatoninergic hexahydroindenopyridines
2014
Hexahydroindenopyridine (HHIP) is an interesting heterocyclic framework that contains an indene core similar to ramelteon. This type of tricyclic piperidines aroused our interest as potential melatoninergic ligands. Melatonin receptor ligands have applications in insomnia and depression. We report herein an efficient two-step method to prepare new HHIP by the reaction of an enamine with 3-bromopropylamine hydrobromide. Some synthesized compounds showed moderate affinity for melatonin receptors in the nanomolar or low micromolar range. Furthermore, the methylenedioxy HHIPs 2d (N-phenylacetamide) and 2f (N,N-diethylacetamide), exhibited high selectivity at MT1 or MT2 receptors, respectively, …
Critical parameters for adduct formation of the carcinogen (+)-anti-benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide with oligonucleotides.
1997
Various parameters relevant for the formation of dG adducts produced in the reaction of individual benzo[a]pyrene diol epoxide (BPDE) stereoisomers with oligonucleotides have been studied. Reaction time, temperature, pH, molar ratio of diol epoxide and oligonucleotide, base sequence, and buffer system were shown to affect the amount of (+)-anti-BPDE dG adducts formed. Optimum experimental conditions for dG adduct formation were different depending on the base sequence context of the oligonucleotide employed [5'-d(CCTATAGATATCC) or 5'-d(CCTATTGCTATCC)]. In general, low temperature to allow a longer reaction time, slightly alkaline Tris-HCl (pH 7.5-8.0) or alkaline phosphate buffer (pH 11), l…
Classification of flavonoid compounds by using entropy of information theory
2013
A total of 74 flavonoid compounds are classified into a periodic table by using an algorithm based on the entropy of information theory. Seven features in hierarchical order are used to classify structurally the flavonoids. From these features, the first three mark the group or column, while the last four are used to indicate the row or period in a table of periodic classification. Those flavonoids in the same group and period are suggested to show maximum similarity in properties. Furthermore, those with only the same group will present moderate similarity. In this report, the flavonoid compounds in the table, whose experimental data in bioactivity and antioxidant properties have been prev…
Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens.
1990
Dibenz(a,h)anthracene (DBA), a carcinogenic, polycyclic aromatic hydrocarbon ubiquitous in the environment, is metabolized by the hepatic microsomal fraction of immature Sprague-Dawley rats pretreated with Aroclor 1254 to 27 ethyl acetate-extractable metabolites. More than half of these metabolites (51%) consisted of trans-1,2-; -3,4-; and -5,6-dihydrodiols including their identified secondary metabolites. The three trans-dihydrodiols (4.9, 15.8, and 0.6% of total metabolic conversion) were highly enriched in their R,R enantiomers (85, 71, and 98%) as determined by high performance liquid chromatography on suitable chiral stationary phases. This is explained on the basis of the stereoselect…
Differential Enantioselectivity of Murine GlutathioneS-Transferase Isoenzymes in the Glutathione Conjugation ofTrans-3,4-dihydroxy-1,2-oxy- 1,2,3,4-t…
1998
Abstract The kinetics of the glutathione (GSH) conjugation of (+)- and (−)-enantiomers ofanti- as well assyn-3,4-dihydroxy-1,2-oxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (B[c]PDE) catalyzed by murine GSHS-transferase (GST) isoenzymes has been investigated. Murine GSTs exhibited significant differences in their enantioselectivity toward B[c]PDE stereoisomers. For example, while pi class isoenzyme mGSTP1-1 was virtually inactive toward stereoisomers with 1Sconfiguration [(−)-syn-and (+)-anti-B[c]PDE], these stereoisomers were good substrates for alpha class isoenzyme mGSTA1-2. When GST activity was measured as a function of varying B[c]PDE concentration (10–320 μM) at a fixed saturating conce…