Carboline Derivatives Research Articles

Recent development of Brensted acid-promoted synthesis of quinoline, isoquinoline and carboline derivatives

Recent development of Brensted acid-promoted synthesis of quinoline, isoquinoline and carboline derivatives

High quantum efficiency and color stability in white phosphorescent organic light-emitting diodes using carboline derivative as a host material

Highly efficient and color stable phosphorescent white organic light-emitting diodes were developed using a high triplet energy host material, 3,3′-bis(9H-pyrido[2,3-b]indol-9-yl)-1,1′-biphenyl (CbBPCb), derived from carboline. Two color phosphorescent white organic light-emitting diodes were fabricated by co-doping of blue and orange triplet emitters or double emitting layer structure of blue and orange emitting layers. High quantum efficiency above 20% and color stability were achieved in the white device by optimizing the doping concentration and emitting layer thickness.

Synthesis and Biological Evaluation of Novel .β-Carboline Derivatives as Antiproliferative Agents

A series of novel β-carboline derivatives was synthesized and evaluated for their cytotoxic activities in vitro against two human tumor cell lines. Most of the compounds showed moderate to potent cytotoxic activities against the tested cell lines, in which compound 12l exhibited the most potent antiproliferative activities against KB cell line (IC50 = 4.58 µM). Preliminary mechanism research on compound 12l indicated that it could inhibit DNA intercalation and tubulin polymerization. Keywords: Antiproliferative, Antitubulin, β-Carboline Derivatives, DNA intercalation, Structure-activity relationship, Synthesis.

Thermally stable carboline derivative as a host material for blue phosphorescent organic light-emitting diodes

A α-carboline based high triplet energy material, 9,9′-(5′-(carbazol-9-yl)-[1,1′:3′,1″-terphenyl]-3,3″-diyl)di-α-carboline (2CbCzT), was designed and synthesized as the thermally stable host material for blue phosphorescent organic light-emitting diodes (PHOLEDs). The 2CbCzT host showed high glass transition temperature of 149°C and high decomposition temperature of 518°C at 5% weight loss. In addition, the 2CbCzT exhibited bipolar charge transport properties due to hole transport type carbazole and electron transport type α-carboline units. Blue PHOLEDs were developed using the high triplet energy 2CbCzT host material and a high quantum efficiency of 22.1% was obtained.

Synthesis of New β-Carboline Derivatives Fused with β-Lactam Rings: An Experimental and Theoretical Study

Synthesis of New β-Carboline Derivatives Fused with β-Lactam Rings: An Experimental and Theoretical Study

P.145L: Late‐News Poster: Synthesis and Device Application of Carboline Derivatives as High Triplet Energy Materials for Blue Phosphorescent OLEDs

AbstractThree carboline derivatives, 9,9′‐m‐phenylenedi‐α‐carboline (NmCP1), 9,9′‐m‐phenylenedi‐β‐carboline (NmCP2), 9,9′‐m‐phenylendi‐γ‐carboline (NmCP3) were synthesized as high triplet energy host materials for blue phosphorescent organic light‐emitting diodes (PHOLEDs). Three carboline derivatives had nitrogen atom at different positions of carboline and the nitrogen atom position was correlated with the photophysical properties and device performances of carboline derivatives.

Pharmacophore Modeling and QSAR Analysis of Novel β-carboline Derivatives as Antitumor Agents

Pharmacophore Modeling and QSAR Analysis of Novel β-carboline Derivatives as Antitumor Agents

Effect of the position of nitrogen in pyridoindole on photophysical properties and device performances of α-, β-, γ-carboline based high triplet energy host materials for deep blue devices

Three carboline derivatives with nitrogen at different positions of the pyridoindole unit were synthesized and the effect of the position of nitrogen on the photophysical properties and device performances was investigated. β-Carboline was effective in obtaining high triplet energy and stabilizing energy levels, while α-carboline was better than other carbolines in terms of quantum efficiency. However, γ-carboline could not stabilize the LUMO level and low quantum efficiency was obtained.

Carboline derivatives with an ortho-linked terphenyl core for high quantum efficiency in blue phosphorescent organic light-emitting diodes

Two host materials, 9-(3''-(9H-carbazol-9-yl)-[1,1':2',1''-terphenyl]-3-yl)-α-carboline (CzOTCb) and 3,3''-bis(α-carbolin-9-yl)-1,1':2',1''-terphenyl (CbOTCb), derived from carboline and ortho-linked terphenyl were synthesized as high triplet energy materials and showed a high triplet energy of 2.90 eV. CzOTCb and CbOTCb were evaluated as the host materials for blue phosphorescent organic light-emitting diodes and high quantum efficiencies of 27.4% and 28.8% were obtained using the CzOTCb and CbOTCb hosts, respectively.

Synthesis and Cytotoxic Activity of New β-Carboline Derivatives

On the basis of harmine and 1-methoxy-canthin-6-one chemical structures, a series of novel 1,4-disubstituted and 1,4,9-trisubstituted β-carbolines and tetracyclic derivatives were designed and synthesized. Cytotoxic activities of these compounds in vitro were investigated in a human tumor cell line panel. Almost all compounds demonstrated interesting cytotoxic activities in particular against prostate cancer cells PC-3 with IC50 in the low micromolar range. Compound X was found to be the most potent one with IC50 value of 8.0 µM; this suggests further studies with models of prostate cancer.

Design, Synthesis and Structure–Activity Relationship of Functionalized Tetrahydro‐β‐carboline Derivatives as Novel PDE5 Inhibitors

Starting from tadalafil as a template, a series of functionalized tetrahydro-β-carboline derivatives have been prepared and identified as novel potent and selective PDE5 inhibitors. Replacing the 3,4-methylenedioxyphenyl at position 6 of tadalafil, together with elongation of the N2-methyl substituent and manipulation of the stereochemical aspects of the two chiral carbons led to the identification of compound XXI, a highly potent PDE5 inhibitor (IC(50) = 3 nM). Compound XXI was also highly selective for PDE5 versus PDE3B, PDE4B, and PDE11A, with a selectivity index of 52 and 235 towards PDE5 rather than PDE11 with both cAMP and cGMP as substrate, respectively.

ChemInform Abstract: Structural Analysis of Carboline Derivatives as Inhibitors of MAPKAP K2 Using 3D QSAR and Docking Studies.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

숙성마늘 extract 의 biomarker로서 생리활성 성분

마늘은 역학조사에 의하면 각종 질환의 예방과 치료에 효능이 있는 것으로 알려져 있다. 마늘의 주요 성분인 알리신 성분은 매우 불안정하여 쉽게 분해되어 새로운 형태의 유황 화합물로 만들어져 이들 성분들이 상승적으로 작용하여 중요한 생리황성을 갖는 것으로 알려져 있다. 시판되고 있는 여러 종류의 마늘제품 중에서 숙성마늘제품이 다른 제품에 비하여 생리활성이 높은 것으로 보고되었다. 숙성마늘제품은 마늘을 일정한 조건으로 숙성시킬 때 수용성 성분인 S-allylcysteine, S-allylmercaptan, steroid saponins, te-trahydro-<TEX>${\beta}$</TEX>-caboline derivatives 및 fructeosyl-arginine 등이 많이 증가하여 그 효능이 상승적으로 높아지는 것으로 알려져 있다. 따라서 시판 마늘가공품의 품질을 표준화하기 위하여 이들 수용성 성분을 biomarker로서 규격기준을 정해야 할 것이다. Garlic (Allium sativum) are an agronomically important genus because of their sulfur flavour components. The majority of the volatiles flavour principles are generated through the enzymatic hydrolysis of the non-volatile organosulfur compounds. However, these compounds may be possible sources of new novel bioacuve and therapeutic principles. Garlic has strong antioxidant activity, and epidemiological studies support the fad that diets rich of garlic may prevent some of the chronic diseases. The health cares of garlic likely arise from a wide variety of components, which may work synergistically. The chemical changes of garlic composition makes it plausible that a variation in processing can lead to acquisition of differential chemical compositions of garlic products. Especially highly unstable allicin can easily disappear during processing and are quickly transformed into a various organosulfur compounds. Various supplements of garlic, particularly aged garlic extract (AGE), are known to possess a promising antioxidant potential and are effective in prevention of chronic diseases because of the bioactive constituents. Although all of active ingredients of AGE are not elucidated, water-soluble components of AGE, including S-allylcysteine, S-allylmercaptane, steroid saponins, tetrahydro-<TEX>${\beta}$</TEX>-carboline derivatives, and fructosyl-arginine, appears to be associated with the pharmacological effects of AGE. Consequently, the allicin free garlic components such as S-allylcysteine, S-allylmercaptane, steroid saponins, tetrahydro-<TEX>${\beta}$</TEX>-carboline derivatives, and fructosyl-arginine can be applicable to standardization of the quality of commercial garlic products. This review provides an insight into garlic's biomarkers and presents evidence that they may either prevent or delay chronic disease associated with aging.

Structural Analysis of Carboline Derivatives As Inhibitors of MAPKAP K2 Using 3D QSAR and Docking Studies

MAPKAPK2, a substrate of p38 MAPKs, plays central role in p38-mediated signal transduction, and its inhibitors are promisingly useful in the treatment of inflammatory diseases. The computational approaches comprising both ligand-based drug design and structure-based drug design were used as virtual screening strategies for the discovery of novel MK2 inhibitors. Two quantitative pharmacophore models were generated with a training set of 27 MK2 inhibitors using HypoGen module of CATALYST. The two models suggested that two hydrogen bond acceptors, one hydrogen bond donor, and one hydrophobic feature are essential for ligand binding. Further, 3D QSAR model with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was constructed using a training set of 42 inhibitors. The predictive CoMFA and CoMSIA models have cross-validated coefficients (q2) of 0.804 and 0.765 and regression coefficients (r2) of 0.984 and 0.986, respectively. The structure-based studies were carried out by docking 77 known MAPKAPK2 inhibitors into the active site of receptor using Glide and analyzing the "hotspots" of the active site. Docking studies revealed that Met138, Leu141, Asp207, Lys93, Cys140, Leu70, Thr206, and Gly143 are showing interactions with highly active compounds. The structure activity relationships elucidated here for carboline derivatives combined with their binding information will provide an integrated approach to explore the chemical space further for improving the potency of MAPKAPK2 inhibitors.

Validation of an ion-pair liquid chromatography–electrospray-tandem mass spectrometry method for the determination of heterocyclic aromatic amines in meat-based infant foods

A method based on ion-pair liquid chromatography–electrospray tandem mass spectrometry (LC–MS/MS) is reported for determining heterocyclic aromatic amines (HAAs) in meat-based infant foods. The HAAs encompassed quinoline (IQ, MeIQ), quinoxaline (MeIQx), pyridine (PhIP), and carboline derivatives (AαC, Harman, Norharman) with d3-IQ, 13C2-MeIQx, and d3-PhIP used as labelled internal standards. The method used extraction into acetone followed by a clean-up on an SCX solid-phase extraction column. LC separation was performed on a TSKgel ODS-80TS column (250 × 2.0 mm, 5 µm), the mobile phase being an ammonium formate–formic acid buffer (3.03 mM ammonium formate, pH = 2.8) aqueous solution–acetonitrile gradient at a flow rate of 0.2 ml min−1. For unequivocal identification of each analyte, three ions were detected and chosen for selected reaction monitoring (SRM). Validation was carried out on lyophilized meat samples. Mean recoveries ranged between 78 ± 4% and 98 ± 2% for different analytes. Limits of quantification generally lower than 8 ng g−1 were demonstrated in meat samples for the analytes investigated. The method exhibited a good linearity and repeatability. Robustness testing identified those factors which were statistically significant in influencing chromatographic separation and response, and indicated which parameters have to be strictly controlled for a reliable analysis of HAAs. In particular, the mobile-phase flow rate was found to be statistically significant (α = 0.05) for the capacity factor (k′) of all analytes except for AαC peak, whereas the mobile-phase pH resulted to be a critical parameter for the k′ values of IQ, MeIQ, and Norharman. The method was proved to be robust vs. resolution between IQ and MeIQ peaks. Among mass-spectrometric parameters, collision energy was found to significantly affect quantitative response of all analytes except that of IQ. The applicability of the method to the analysis of meat-based infant food samples was demonstrated.

An unusual hydrogen addition of indolo-2,3-quinodimethanes to dimethylindoles in the presence of 1,3-azoles

Indolo-2,3-quinodimethane generatedin situ frombis-(bromomethyl)indole with NaI/DMF at 70°C was expected to undergo cycloaddition with 1,3-azoles to give carboline derivatives, which form the backbone of many indole alkaloids. However, the reaction did not give the anticipated product but proceeded via hydrogen addition to exocyclic methylene groups, furnishing dimethylindoles in good yields

Electronic spectroscopy of the β-carboline derivatives nitronorharmanes, nitroharmanes, nitroharmines and chloroharmines in homogeneous media and in solid matrix

Electronic spectra (absorption, fluorescence and phosphorescence emission spectra) of nitro-β- carboline derivatives (nitronorharmanes, nitroharmanes and nitroharmines) in acetonitrile and in methanol solution at 298 K and in solid matrix at 77 K have been recorded and compared with those of the corresponding β-carbolines and chloroharmine derivatives. The electronic absorption spectra of triplet transients of these β-carbolines, the triplet lifetime, τT, and the intersystem crossing quantum yield, φisc, were measured by Laser Flash Photolysis at 298 K. The dynamic properties of the lowest excited singlet and triplet states (τf, τp, φf and φp) have been measured in the same experimental conditions. From these data, the radiative and radiationless rate constants (k o f , kisc and kic) were derived. The intramolecular spin - orbital coupling effect on the spectroscopic data and photophysical rate constant were also analyzed.

Selected Recent Advances in the Stereoselective Synthesis of Isoquinoline and &amp;#946;-Carboline Derivatives with the Use of Chiral Auxiliaries of Natural Origin

Selected Recent Advances in the Stereoselective Synthesis of Isoquinoline and &amp;#946;-Carboline Derivatives with the Use of Chiral Auxiliaries of Natural Origin

Investigation of the separation of heterocyclic aromatic amines by reversed phase ion-pair liquid chromatography coupled with tandem mass spectrometry: The role of ion pair reagents on LC–MS/MS sensitivity

Reversed phase ion-pair chromatography (RP-IPC) of seven heterocyclic aromatic amines encompassing quinoline (IQ, MeIQ), quinoxaline (MeIQx), pyridine (PhIP) and carboline derivatives (AalphaC, Harman, Norharman) was carried out with formate as counter ion in an aqueous eluent with acetonitrile as organic modifier. TSKgel ODS-80TS was used as the stationary phase. With the aim of acquiring a better insight into the mutual influence of ion-pair reagent and the organic modifier upon solute retention, the study was performed by using an experimental design approach able to evidencing the effect of the simultaneous variation of the two factors. A model for the chromatographic behavior of the amines is proposed that includes classical ion-pair mechanism involving formate in the case of MeIQx, PhIP, Harman and Norharman. A competitive ion-exchange mechanism was hypothesized to govern retention of quinoline compounds, whereas electrostatic interactions and hydrogen bond formation with the silanols of the stationary phase were judged to be responsible for the retention of AalphaC. Further, the chromatographic behavior of the analytes using the formic acid-ammonium formate buffer in the mobile phase was compared with that observed using acetic acid-ammonium acetate buffer. The method based on the use of RP IPC with tandem mass spectrometry when the eluent contained formate buffer at pH 2.8 exhibited higher detectability with respect to that achieved using the acetate buffer.

Synthesis and biological evaluation of novel $beta;-carboline derivatives as Tat?TAR interaction inhibitors

Synthesis and biological evaluation of novel $beta;-carboline derivatives as Tat?TAR interaction inhibitors