42438-90-4Relevant articles and documents
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.
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
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
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.
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.
