1085709-06-3

Upstream product

• 113247-18-0 1-(4-methoxyphenyl)-β-carboline-3-carboxylic acid methyl ester 
• 942217-34-7 1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylic acid 
• 123-11-5 4-methoxy-benzaldehyde 
• 73-22-3 L-Tryptophan 
• 4299-70-1 L-tryptophan methyl ester 
• 324518-45-8 (3S)-1-(4-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid 
• 243842-55-9 (3S)-1-(4-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester 
• 82789-20-6 1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid 
• 68014-36-8 methyl 1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 
• 54-12-6 Trp 
• 1262841-96-2 ethyl 1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate 

Downstream Products

• 1085708-77-5 1-(4-methoxyphenyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl)-9H-pyrido[3,4-b]indole 
• 1085708-95-7 1-(4-methoxyphenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) β-carboline 
• 1198097-76-5 1-(4-methoxyphenyl)-N'-(4-nitrobenzylidene)-9H-pyrido[3,4-b]indole-3-carbohydrazide 
• 1198097-75-4 1-(4-methoxyphenyl)-N'-benzylidene-9H-pyrido[3,4-b]indole-3-carbohydrazide 
• 1198097-73-2 1-(4-methoxyphenyl)-N'-(4-methoxybenzylidene)-9H-pyrido[3,4-b]indole-3-carbohydrazide 
• 1198097-74-3 1-(4-methoxyphenyl)-N'-(4-N,N-dimethylaminobenzylidene)-9H-pyrido[3,4-b]indole-3-carbohydrazide 
• 1345667-65-3 N'-cyclohexylidene-1-(4-methoxyphenyl)-β-carboline-3-carbohydrazide 
• 1345667-72-2 N'-cyclopentylidene-1-(4-methoxyphenyl)-β-carboline-3-carbohydrazide 
• 1345667-79-9 N'-2-propylidene-1-(4-methoxyphenyl)-β-carboline-3-carbohydrazide 

Relevant academic research and scientific papers

Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells

A series of novel β-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these β-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53–1.56 μM, which was considerably more potent than harmine (IC50 = 46.7–55.3 μM) and also three-to ten-fold lower than that of SAHA (IC50 = 4.48–6.26 μM). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and α-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway.

Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives

A series of methyl β-carboline carboxylates (2a-g) and of imide-β-carboline derivatives containing the phthalimide (4a-g), maleimide (5b, g) and succinimide (6b, e, g) moiety were synthesized, and evaluated for their activity against Mycobacterium tuberculosis H37Rv. The most active β-carboline derivatives against the reference strain were assayed for their cytotoxicity and the activity against resistant M. tuberculosis clinical isolates. Farther, structure-activity relationship (SAR) studies were carried out using the three and four-dimensional approaches for starting to understand the way of β-carboline activity in M. tuberculosis. All 19 β-carboline derivatives were assayed, firstly, by determining the minimum inhibitory concentration (MIC) using resazurin microtiter assay plate (REMA) in M. tuberculosis H37Rv. Then, five derivatives (2c, 4a, 4e, 4g, 6g), which showed MIC ≤ 125 μg/mL, were assayed in nine resistant M. tuberculosis clinical isolates (five MDR, three isoniazid monoresistant and one isoniazid plus streptomycin resistant). The MIC values against the resistant clinical isolates ranged from 31.25 to >250 μg/mL. All five derivatives were non-cytotoxic to the VERO cell line, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, at the tested concentration (selectivity index ranged from 1.74 to 14.4). Our study demonstrated that (2c) and (6g) derivatives had better anti-M. tuberculosis activity, especially against resistant clinical isolates, what makes them scaffold candidates for further investigations about their anti-tuberculosis activity. The SAR study conducted with the 19 β-carboline derivatives showed the importance of steric effects for the synthesized β-carbolines against M tuberculosis, and these models can be used for future proposition of new derivatives, increasing the chances of obtaining potentially anti-tuberculosis compounds.

Beta-carboline-cycloenone derivative based on dual response to pH value and GSH and application thereof

The invention discloses a beta-carboline-cycloenone derivative with a structure as shown in a general formula which is described in the specification. According to the invention, an electron-donatinggroup is introduced into a proper part of beta-carboline, and the 3-site amino group of beta-carboline is connected with cycloenone having anti-tumor activity by utilizing a carbamate bond, so the novel beta-carboline-cycloenone derivative is designed and synthesized. The derivative realizes pH and GSH dual-response fluorescence imaging and diagnosis in a tumor microenvironment, and can selectively target to GSTpi highly-expressed in tumor tissue, so tumor cell proliferation can be significantly inhibited. Such a pH/GSH dual-response fluorescence and cancer-targeting treatment diagnosis and treatment drug provides a new choice for accurate diagnosis and targeting treatment of tumors, and broadens the application of multifunctional molecules in accurate medical treatment.

Hydroxamic Acid Derivatives of β-Carboline/Hydroxycinnamic Acid Hybrids Inducing Apoptosis and Autophagy through the PI3K/Akt/mTOR Pathways

Naturally occurring β-carbolines are known to have antitumor activities but with limited effectiveness. In order to improve their efficacy, a series of new hydroxamic-acid-containing β-carbolines connected via a hydroxycinnamic acid moitey (12a-f) were developed to incorporate histone deacetylase (HDAC) inhibition for possible synergistic effects. When evaluated in in vitro assays, most of the analogues showed significant antitumor activities against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin and induced greater cancer cell apoptosis than the FDA-approved HDAC inhibitor SAHA by regulating expression of apoptotic proteins Bax, Bcl-2, and caspase 3. Importantly, 12b also induced a significant amount of autophagic flux activity in Bel7402 cells by increasing the expression of Beclin-1 and LC3-II proteins and decreasing that of LC3-I and p62. Finally, 12b significantly inhibited PI3K/Akt/mTOR signaling, an important cell-growth-promoting pathway aberrantly activated in many cancers. Together, the results suggest that these hydroxamic-acid-containing β-carboline derivatives may be new leads for the discovery of agents for the treatment of human carcinoma cancers.

Design, synthesis, and biological evaluation of novel N-acylhydrazone bond linked heterobivalent β-carbolines as potential anticancer agents

Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 ± 0.9, 8.6 ± 1.4, 6.2 ± 2.5, 9.9 ± 0.5, and 5.7 ± 1.2 μM against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent β-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.

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.

Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids

A series of novel hybrids β-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 μM. Compounds 9e and 16b were also active against amastigote forms, displaying IC50 values of 1.0 ± 0.1 μM and 1.2 ± 0.5 μM, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of β-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death.

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.

Synthesis and evaluation of novel hybrids β-carboline-4-thiazolidinones as potential antitumor and antiviral agents

A series of novel hybrids β-carboline-4-thiazolidinones were synthesized and evaluated for their in vitro antitumor activity against human cancer cell lines and for antiviral activity towards Herpes simplex virus type-1 (HSV-1). From the N′-(2-ylidene-4-thiazolidinone)-β-carboline-3-carbohydrazide series (9–11), compounds 9c and 11d were the most active, showing growth inhibition 50% (GI50) values less than 5 μM for all cell lines tested. Compound 9c, bearing the 4-dimethylaminophenyl group at C-1 of β-carboline was selected for further investigation concerning cell death and cell cycle profile, focusing on the human renal adenocarcinoma cell line 786-0. Treatments with 25 μM of compound 9c induced cell death after 15 h of treatment, characterized by phosphatidylserine exposure and loss of membrane integrity. Moreover, treatment with 12.5 μM promoted a sub-G1 arrest, which indicates cell death. Derivatives of the N-(2-substituted-aryl-4-thiazolidinone)-β-carboline-3-carboxamide series (18–23) showed a potent activity and high selectivity for glioma (U251) and ovarian (OVCAR-3) cancer cell lines. Also, some β-carboline-4-thiazolidinone hybrids showed potent antiviral activity against Herpes simplex virus type-1. The N-(2-substituted-aryl-4-thiazolidinone)-carboxamide moiety in 18, 19 and 22 confer a potent anti-HSV-1 activity for these derivatives, which presented EC50values of 0.80, 2.15 and 2.02 μM, respectively. The assay results showed that the nature of 4-thiazolidinone moiety and of the substituent attached at the 3- and 1- position of β-carboline nucleus influenced the antitumor and antiviral activities.

Containing β-Carboline-3- [...] the HDAC inhibitor and its preparation and use

The invention discloses an HDAC (histone deacetylase) inhibitor containing beta- carboline-3-acryl hydrazono as well as a preparation method and application thereof. A product has a structure as shown in structural formula I; the HDAC inhibitor can be applied as a drug for treating and/or preventing tumors such as liver cancer, pancreatic cancer, colon cancer, lung cancer, stomach cancer, breast cancer, ovarian cancer, and the like.