42438-90-4Relevant academic research and scientific papers
Design, synthesis and evaluation of a novel π-π Stacking nano-intercalator as an anti-tumor agent
Zhu, Haimei,Song, Yuanbo,Wang, Yuji,Zhao, Ming,Ren, Yi,Wang, Yaonan,Zhao, Shurui,Wu, Jianhui,Peng, Shiqi
, p. 247 - 257 (2016)
Based on the knowledge that cyclohexane-1,4-dione, piperazine and β-carboline are the essential building blocks of DNA intercalators, β-carboline-3-carboxylic acid is a π-π stack-like DNA intercalator, and β-carboline derivatives can form nanoparticles, this paper hypothesized that (2′S,5′S)-tetrahydropyrazino[1′,2′:1,6]- di{2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole}-1′,4′-dione (THPDTPI) would be a π-π stacking lead nano-intercalator. The docking investigation found that THPDTPI can intercalate into DNA in a π-π stacking manner. The simple condensation of 3S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid provided THPDTPI in good yield and high purity. The TEM, SEM and AFM imaging visualized that THPDTPI formed nanoparticles in ultrapure water, in the solid state and in rat plasma. The Faraday-Tyndall effect proved that THPDTPI exhibited nano-properties in pH 2.0 and pH 7.0 water. Spectrophotometric assays suggested that the interaction model of THPDTPI and CT DNA was π-π stacking intercalation. In vivo THPDTPI dose-dependently slowed the tumor growth of S180 mice with a minimal effective dose of 0.01 μmol kg-1 per day. In vitro THPDTPI exhibited anti-proliferation activities on S180 and HeLa cells with IC50 values of 0.39 and 3.5 μM, respectively. Even when the single dose was raised up to 10 000 fold of the minimal effective dose, i.e. 100 μmol kg-1, THPDTPI still did not show liver, kidney and systemic toxicity in mice. These findings provide a strategy for designing THPDTPI-like π-π stacking nano-intercalators.
Fluorescence of a rotationally constrained tryptophan derivative, 3-carboxy-1,2,3,4-tetrahydro-2-carboline
Tilstra, Luanne,Sattler, Melissa C.,Cherry, William R.,Barkley, Mary D.
, p. 9176 - 9182 (1990)
Despite a plethora of work on tryptophan photophysics, the origin of the complex fluorescence decay kinetics is still unknown. A question remains whether the two fluorescence lifetimes of the tryptophan zwitterion are due to ground-state and therefore excited-state heterogeneity resulting from rotameric forms. To test the conformer model, we synthesized a tryptophan derivative, 3-carboxy-1,2,3,4-tetrahydro-2-carboline, which restricts rotation of the alanyl side chain. The constraint limits the number of conformations available to the molecule without greatly affecting the electronic properties. The absorption and emission spectra and the pK of the amino group are similar to those of tryptophan. The fluorescence decay of the constrained derivative is an apparent monoexponential. The zwitterion has a lifetime of 6.2 ± 0.2 ns and the anion has a lifetime of 4.7 ± 0.2 ns at 25°C. Global analysis of time-resolved emission spectral data for the zwitterion reveals a double-exponential decay, which may reflect two stable conformations of the partially unsaturated six-membered ring. This is discussed in detail in the following paper.
Synthesis and crystal structure analysis of 9-phenyl-β-carboline
Meesala, Ramu,Mordi, Mohd Nizam,Mansor, Sharif Mahsufi,Rosli, Mohd Mustaqim
, p. 125 - 134 (2014)
An efficient method is described for the synthesis of 9-phenyl-9H-pyrido[3,4-b]indole and 9-(4-chlorophenyl)-9H-pyrido[3,4-b]indole by employing a catalytic amount of CuI (10 mole%) without any ligand. The single crystal of 9-phenyl-9H-pyrido[3,4-b]indole
Histone demethylating agents as potential S-adenosyl-l-methionine-competitors
Navakauskiene,Mori,Christodoulou,Zentelyte,Botta,Via, L. Dalla,Ricci,Damia,Passarella,Zilio,Martinet
, p. 1245 - 1255 (2016)
Histone H3 methylation on K9 and/or K27 depends on histone lysine methyltransferases (KMTs). EZH2, one of the components of the PRC2 complex, catalyzes the trimethylation of histone H3K27, which is associated with transcriptional repression and tumor development. H3K9me3 mediated gene silencing may result from other KDMs such as G9a/GLP, SUV39H1-2, SETDB1, CCLD8 and RIZ1. Their disturbance leads to defective cell mitosis. It is therefore desirable to find small molecules that are able to decrease H3K9 and K27 tagging to reinitiate gene transcription. Most KDM inhibitors are still based on SAM co-factor competition/modulation. Herein, functional screening of a diversity library proved to be a useful tool for finding new specific KDM inhibitors; the use of SAM-based pharmacophoric models facilitated the understanding of their possible mechanism of action.
Highly diastereoselective synthesis of 1-carbamoyl-4-aminoindoloazepinone derivatives via the Ugi reaction
Jida, Mouhamad,Betti, Cecilia,Urbanczyk-Lipkowska, Zofia,Tourwe, Dirk,Ballet, Steven
, p. 5866 - 5869 (2013)
A one-pot procedure for the highly diastereoselective synthesis of 1-carbamoyl-4-amino-1,2,4,5-tetrahydroindolo[2,3-c]azepin-3-one derivatives is described. Using 2-formyl-L-tryptophan as a bifunctional building block, a catalyst-free Ugi-three-component
Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect
Zheng, Hongbo,Wu, Yifeng,Sun, Bin,Cheng, Chuanle,Qiao, Yanan,Jiang, Yuehua,Zhao, Shengtian,Xie, Zhiyu,Tan, Jing,Lou, Hongxiang
, p. 767 - 780 (2018)
Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-β-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-β-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-β-carboline-piperazinedione 19f and tetrahydro-β-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110–150 μm) via NO–sGC–cGMP pathway, implying their further application for the treatment of vascular diseases.
Structure-based discovery of (S)-2-amino-6-(4-fluorobenzyl)-5,6,11,11a-tetrahydro-1H-imidazo[1′,5′:1,6]pyrido[3,4-b]indole-1,3(2H)-dione as low nanomolar, orally bioavailable autotaxin inhibitor
Roy, Ashis,Sarkar, Tonmoy,Datta, Sebak,Maiti, Arup,Chakrabarti, Monali,Mondal, Trisha,Mondal, Chaitali,Banerjee, Apurba,Roy, Subhasis,Mukherjee, Soumen,Muley, Pragati,Chakraborty, Sabyasachi,Banerjee, Manish,Kundu, Mrinalkanti,Roy, Kuldeep K.
, p. 496 - 503 (2022/01/08)
Inhibition of extracellular secreted enzyme autotaxin (ATX) represents an attractive strategy for the development of new therapeutics to treat various diseases and a few inhibitors entered in clinical trials. We herein describe structure-based design, syn
Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids
He, Ling,Jiang, Yan,Qiao, Zhen,Qiu, Hanyue,Su, Xiaojiao,Tan, Qiuyuan,Yang, Jiaojiao,Yang, Zhao,Zhang, Min,Zhou, Wenqiang
supporting information, p. 13105 - 13111 (2021/05/10)
We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L-tryptophan as the starting material. Two key bridged skeleton-forming reactions, namely tandem sequential oxidative cyclopropanol ring-opening cyclization and ketone α-allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na-methyl-16-epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N-demethylkoumine) with more complex cage scaffolds has been accomplished.
NITROGEN-CONTAINING COMPOUND, METHOD FOR MANUFACTURING THE SAME, AND OPTICAL FUNCTIONAL MATERIAL INCLUDING THE SAME
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Paragraph 0144-0145, (2021/08/21)
PROBLEM TO BE SOLVED: To provide a novel nitrogen-containing compound having luminescence property. SOLUTION: A nitrogen-containing compound represented by the following formula (I) in which RA, RB, R1, R2, R3, R4, and X are either one of the following (1) and (2). SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
Nanoparticles of a new small-molecule P-selectin inhibitor attenuate thrombosis, inflammation, and tumor growth in two animal models
Feng, Qiqi,Wang, Mengyang,Muhtar, Eldar,Wang, Yaonan,Zhu, Haimei
, p. 5777 - 5795 (2021/09/03)
Purpose: To assess whether the newly designed small-molecule oral P-selectin inhibitor 3S-1,2,3,4-tetrahydro-β-carboline-3-methyl aspartyl ester (THCMA) as a nanomedicine enhances antithrombosis, anti-inflammation, and antitumor activity more than the clinical trial drug PSI-697. Methods: THCMA was designed as an amphiphile containing pharmacophores of PSI-697. Its nanofeatures were explored with TEM, SEM, Tyndall effect, ζ-potential, FT-ICR-MS, and NOESY 2D1H NMR. The P-selectin inhibitory effect of THCMA was demonstrated with molecular docking, ultraviolet (UV) spectra, and competitive ELISA. In vivo and in vitro assays — anti-arterial thrombosis, anti–venous thrombosis, anti-inflammation, antitumor growth, anti–platelet aggregation, rat-tail bleeding time, anticoagulation index, soluble P-selectin (sP-selectin) expression, and serum TNFα expression — were performed to explore bioactivity and potential mechanisms. Water solubility of THCMA was measured using UV-absorption spectra. Results: THCMA self-assembled into nanorings of approximately 100 nm in diameter. Its water solubility was about 1,030-fold that of PSI-697. THCMA exhibited more potent P-selectin inhibitory effect than PSI-697. The oral efficacy of THCMA was 100-fold that of PSI-697 in inhibiting arterial and venous thrombosis and tenfold in inhibiting inflamma-tion. THCMA inhibited thrombosis at a dose that produces no coagulation disorders and no bleeding risk. THCMA exhibited enhanced antitumor activity over PSI-697 without systemic chemotherapy toxicity. THCMA significantly inhibited platelet aggregation in vitro and downregulated the expression levels of serum sP-selectin and TNFα in vivo. Conclusion: A new small-molecule P-selectin inhibitor, THCMA, has been successfully designed as a nanomedicine with largely enhanced oral efficacy compared to the clinical trial drug PSI-697, and thus might be developed for the oral treatment of arterial thrombosis, venous thrombosis, inflammation, and cancer-associated thrombosis.
