68014-36-8

Upstream product

• 123-11-5 4-methoxy-benzaldehyde 
• 4299-70-1 L-tryptophan methyl ester 
• 5619-09-0 methyl tryptophanate hydrochloride 
• 73-22-3 L-Tryptophan 
• 7303-49-3 DL-tryptophan methyl ester 
• 67-56-1 methanol 
• 82789-20-6 1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid 
• 54-12-6 Trp 

Downstream Products

• 1262842-24-9 C₂₇H₂₆N₂O₅S 
• 1585210-51-0 1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde 
• 1085709-06-3 1-(4-methoxyphenyl)-β-carboline-3-carboxylic acid hydrazide 

Relevant academic research and scientific papers

Synthesis of tetrahydro-β-carbolinediketopiperazines in [bdmim][PF6] ionic liquid accelerated by controlled microwave heating

Because of their negligible vapor pressures and large dipoles, ionic liquids are excellent media for microwave-accelerated organic reactions. Using low-power microwave irradiation in the new [bdmim][PF6] ionic liquid with temperature controlled at 60°C, a three-step synthesis (Pictet-Spengler, Schotten-Baumann, and intramolecular ester amidation) of tetrahydro-β-carbolinediketopiperazines starting from tryptophan methyl ester was achieved with good isolated yields (49-69%) in only 5 min.

β-Carboline tethered cinnamoyl 2-aminobenzamides as class I selective HDAC inhibitors: Design, synthesis, biological activities and modelling studies

The effect of β-carboline motif as cap for HDAC inhibitors containing cinnamic acid as linker and benzamides as zinc binding group was examined in this study. A series of β-carboline-cinnamide conjugates have been synthesized and evaluated for their HDAC inhibitory activity and in vitro cytotoxicity against different human cancer cell lines. Almost all the compounds exhibited superior HDAC inhibitory activity than the standard drug Entinostat for in vitro enzymatic assay. Among the tested compounds, 7h displayed a noteworthy potency with an IC50 value of 0.70 ± 0.15 μM against HCT-15 cell line when compared to the standard drug Entinostat (IC50 of 3.87 ± 0.62 μM). The traditional apoptosis assays such as nuclear morphological alterations, AO/EB, DAPI, and Annexin-V/PI staining revealed the antiproliferative activity of 7h while depolarization of mitochondrial membrane potential by JC-1 was observed in dose-dependent manner. Cell cycle analysis also unveiled the typical accumulation of cells in G2M phase and sub-G1/S phase arrest. In addition, immunoblot analysis for compound 7h on HCT-15 indicated selective inhibition of the protein expression of class I HDAC 2 and 3 isoforms. Molecular docking analysis of compound 7h revealed that it can prominent binding with the active pocket of the HDAC 2. These finding suggest that the compound 7h can be a promising lead candidate for further investigation in the development of novel anti-cancer drug potentially inhibiting HDACs.

Synthesis, Antileishmanial Activity and Spin Labeling EPR Studies of Novel β-Carboline-Oxazoline and β-Carboline-Dihydrooxazine Derivatives

A series of novel 1-(substituted-phenyl)-3-(4,5-dihydro-1,3-oxazol-2-yl)-9H-β-carboline (8a-8i) and 1-(substituted-phenyl)-3-(5,6-dihydro-4H-1,3-oxazin-2-yl)-9H-β-carboline (9a-9h) derivatives, as well as their respective N-(chloroalkyl)-1-(substituted-phenyl)-9H-β-carboline-3-carboxamide precursors (6a-6i and 7a-7h), were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. Compounds 8d, 8i, 9e and 9h exhibited significant activity for both promastigote and amastigote forms, with IC50 (50% inhibitory concentration) values ranging from 2.9 to 23.0 μM. In addition, spin label electron paramagnetic resonance (EPR) spectroscopy studies were carried out for the most active compounds against L. amazonensis promastigotes. The studies indicated that the tested compounds cause strong stiffness in the parasite plasma membrane and are capable of inducing internal metalloproteins oxidation of the parasite, resulting in their cross-linking to skeletal proteins. Compounds 8d and 8i produced the largest effect, showing that the presence of oxazoline group at C-3 of β-carboline nucleus is important for antileishmanial activity.

Novel β-carboline-based indole-4,7-quinone derivatives as NAD(P)H: Quinone-oxidoreductase-1 inhibitor with potent antitumor activities by inducing reactive oxygen species, apoptosis, and DNA damage

Eighteen new β-carboline-based indole-4,7-quinone derivatives (12a–i and 13a–i) were designed and synthesized, and their in vitro and in vivo antiproliferative activities were studied. Most of target compounds showed strong inhibition on three human tumor cells' proliferation. In particular, the most active compound 13g not only displayed more prominent antiproliferative activities than β-lapachone, a clinical antitumor candidate, but also exerted significant NAD(P)H: quinone-oxidoreductase-1 (NQO1) inhibitory activity and NQO1-dependent cytotoxicity in HT29 cells. Furthermore, 13g dose-dependently induced high ROS levels in HT29 cells, and selectively inhibited cancer cell but not non-tumor colon cell proliferation in vitro. Importantly, 13g promoted HT29 cell apoptosis and DNA damage by regulating relative apoptotic proteins and H2AX expression. Finally, 13g displayed significant growth inhibition of HT29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.

Bimetallic catalyzed N-arylation used in synthesis of novel β-carbolines derivatives

Background: Natural occurring β-Carbolines alkaloids are abundant in the plant king-dom or other organisms, and they were found to possess good antitumor activity through multiple mechanisms. Based on previous summarized SARs of β-carboline derivatives, t

β-Carboline and N-hydroxycinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma

In an effort to develop anticancer agents that may overcome drug resistance, the number one reason in caner death, we have developed a series of novel hybrids of β-carboline and N-hydroxycinnamamide as histone deacetylase (HDAC) inhibitors. Most of the hybrids 13a-p showed strong antiproliferative effects with low-micromolar IC50 values against four human cancer cells. The most potent compound of series 13p exhibited high HDAC1/6 inhibitory effects, and also increased the acetylation levels of histone H3, H4 and α-tubulin. Importantly, 13p demonstrated high anticancer potency against drug-sensitive HepG2 and Bel7402 cells and drug-resistant Bel7402/5FU cells. Hybrid 13p triggered significant apoptosis by regulating apoptotic relative proteins expression in these Bel7402/5FU cells. Finally, 13p induced a substantial amount of autophagic flux activity by the accretion of the expression of LC3-II and the degeneration of expression of p62 and LC3-I in Bel7402/5FU cells. Overall, 13p is a novel β-carboline/N-hydroxycinnamamide hybrid with significant anticancer potency that warrants further evaluation for the treatment of drug-resistant hepatocellular carcinoma.

Cu-catalyzed mild and efficient oxidation of THβCs using air: Application in practical total syntheses of perlolyrine and flazin

A mild, efficient and environmentally benign method for synthesis of aromatic β-carbolines via Cu(ii)-catalyzed oxidation of 1,2,3,4-tetrahydro-β-carbolines (THβCs) was developed, in which air (O2) was used as the clean oxidant. This method has advantages such as environmentally friendliness, mildness, very good tolerance of functional groups, high yielding and easy experiment operation. In addition, this new methodology was successfully applied in the efficient and practical total syntheses of β-carboline alkaloids perlolyrine and flazin.

METHOD OF SCREENING FOR AGENTS FOR DIFFERENTIATING STEM CELLS

The present application discloses a method for identifying an agent for the treatment or prevention of cancer or metastatic cancer comprising the steps of contacting stem cell with a potential agent, and identifying an agent that induces differentiation, or inhibits stem cell pluripotency or growth of the stem cell, wherein such agent is determined to be an anti-cancer agent.

Beta-carboline derivative targeted to CDK and DNA and preparation method and medical application thereof

The invention discloses a beta-carboline derivative targeted to CDK and DNA and a preparation method and medical application thereof. The beta-carboline derivative has a structure shown in the general formula I in the description. The compound can be applied in combination with other antitumor drugs and can also be applied in combination with radiotherapy. The antitumor drugs or radiotherapy and the compound can be applied at the same time or at different times. The combined therapy can perform a synergistic effect, and thus the therapeutic effect can be easily improved.

Simple and efficient method for aromatization of tetrahydro-β-carbolines by using K2S2O8 as a catalyst and its antimicrobial activity comparison with molecular docking studies

A novel and efficient aromatization of tetrahydro-β-carbolines under mild conditions using K2S2O8 as a catalyst was developed. The method is applicable for all kinds of C1 substituted systems. All synthesized compounds were screened for their in vitro antibacterial activity against Staphylococus aureus, Bacillus subtilis, Escherichia coli, and Klebsiella pneumonia, as well as fungi, such as Aspergillus flavus and Fusarium oxysporum. Compounds 4b, 4g, 4i, and 4k demonstrated excellent in vitro antibacterial and antifungal activities than the standard drugs. The docking studies were carried out for most active compounds 4b, 4g, 4i, and 4k.