113247-16-8

Basic information

• Product Name: 9H-Pyrido[3,4-b]indole-3-carboxylic acid, 1-(4-chlorophenyl)-, methyl ester
• CAS NO: 113247-16-8
• Molecular Formula: C19H13ClN2O2
• Molecular Weight: 336.777
• Mol File: 113247-16-8.mol

Chemical Properties

• CAS DataBase Reference: 9H-Pyrido[3,4-b]indole-3-carboxylic acid, 1-(4-chlorophenyl)-, methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 9H-Pyrido[3,4-b]indole-3-carboxylic acid, 1-(4-chlorophenyl)-, methyl ester(113247-16-8)
• EPA Substance Registry System: 9H-Pyrido[3,4-b]indole-3-carboxylic acid, 1-(4-chlorophenyl)-, methyl ester(113247-16-8)

Safety Data

• Hazardous Substances Data: 113247-16-8(Hazardous Substances Data)

Upstream product

• 74-88-4 methyl iodide 
• 104-88-1 4-chlorobenzaldehyde 
• 5619-09-0 methyl tryptophanate hydrochloride 
• 54-12-6 Trp 
• 7524-52-9 (S)-tryptophan methyl ester hydrochloride 
• 4299-70-1 L-tryptophan methyl ester 
• 7303-49-3 DL-tryptophan methyl ester 
• 865619-24-5 1-(4-chloro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 
• 73-22-3 L-Tryptophan 
• 238428-08-5 (1S,3S)-methyl 1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 
• 82789-40-0 methyl-1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 

Downstream Products

• 1401863-55-5 N-(2-aminoethyl)-1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide hydrochloride 

Relevant articles and documents

Design and Synthesis of DNA-Interactive β-Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis-Inducing Agents

A new series of (E)-3-[(1-aryl-9H-pyrido[3,4-b]indol-3-yl)methylene]indolin-2-one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT-15, HCT-116, A549, NCI-H460, and MCF-7, including HFL. Among the tested compounds, (E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one (10 s) showed potent cytotoxicity against HCT-15 cancer cells with an IC50 value of 1.43±0.26 μm and a GI50 value of 0.89±0.06 μm. Notably, induction of apoptosis by 10 s on the HCT-15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V-FITC/PI, DCFDA, and JC-1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT-15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT-15 cancer cells led to decreased expression of anti-apoptotic Bcl-2 and increased protein expression of both pro-apoptotic Bax and caspase-3, -8, and -9, and cleaved PARP with reference to actin. Next, a clonogenic assay revealed the inhibition of colony formation in HCT-15 cancer cells by 10 s in a dose-dependent manner. Moreover, upon testing on normal human lung cells (HFL), the compounds were observed to be safer with a low toxicity profile. In addition, viscosity and molecular-docking studies showed that compound 10 s has typical intercalation with DNA.

In(OTf)3 assisted synthesis of β-carboline C-3 tethered imidazo[1,2-a]azine derivatives

Synthesis of β-carboline based natural products and synthetic derivatives is one of the frontier areas of research owing to their medicinal properties. It is envisaged that 3-formyl-9H-β-carboline is a potential precursor and offers new vistas for the construction of a variety of heterocyclic architectures at the C-3 position of the β-carboline skeleton. In this context, an efficient protocol has been developed for the synthesis of β-carboline C-3 tethered imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[1,2-a]pyrazine derivatives via exploration of the Groebke-Blackburn-Bienayme (GBB) reaction. The present protocol offers several advantages like operational simplicity, high atom economy, appreciable structural diversity and easy purification procedure.

Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity, DNA-binding ability, viscosity and molecular modeling studies

A series of new DNA-interactive C3-tethered 1,2,3-triazolo-β-carboline derivatives have been synthesized via 'click' reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. Interestingly, these hybrids have displayed potent in vitro cytotoxicity in comparison to Harmine against the HT-29 (colon cancer) and HGC-27 (gastric cancer) cell lines. The compounds 7f, 7k, 7n and 7s appear to be more effective against the HGC-27 cell line, among which compound 7f showed the highest cytotoxicity (5.44 ± 0.58, IC50 μM). The compounds 7e and 7f appear to be more active against the HT-29 cell line, among which compound 7f exhibited the highest cytotoxicity (3.67 ± 0.62, IC50 μM). To gain more insight into the DNA-binding ability, spectroscopic techniques such as UV-Visible, fluorescence and circular dichroism studies were performed. Viscosity measurements and molecular docking studies substantiate that these compounds indeed bind to DNA via the minor groove.

Development of β-carboline-benzothiazole hybrids via carboxamide formation as cytotoxic agents: DNA intercalative topoisomerase IIα inhibition and apoptosis induction

In quest of promising anticancer agents, the pharmacophores of natural (β-carboline) and synthetic origin (benzothiazole) were adjoined by a carboxamide bridge and three-point diversification was accomplished. The in vitro cytotoxic ability of the compounds was established on adherent and suspension human cancer cell lines and compounds 8u and 8f advanced as pre-eminent molecules with IC50 values of 1.46 and 1.81 μM respectively in A549 cell line. The cytospecificity was entrenched for potent compounds 8u and 8f by evaluating against normal human lung epithelial cells and selectivity index was calculated. Furthermore, EtBr displacement, relative viscosity and gel-based topoisomerase II target assays unveiled the intercalative topo-II inhibitory capability and DNA binding studies (absorbance) revealed the dissociation constant (Kd) for compounds 8u and 8f as 98 and 103 μM respectively. Additionally, cell-based flow cytometric assays like Annexin-V/PI dual staining aids in the quantification of apoptosis induced and JC-1 staining disclosed the depolarization of mitochondrial membrane potential by compound 8u in A549 cells in a dose-dependent manner. Moreover, wound healing assay established the inhibition of in vitro cell migration by compound 8u on A549 cells. In addition, molecular docking studies proved the binding of compounds 8u and 8f in the active site of DNA complexed with topo IIα and stabilized by interactions with DNA base pairs and amino acid residues. Remarkably, the compounds 8u and 8f follow Lipinski's rule of five and are in the recommended range for Jorgensen's rule of three with a minimal violation and other pharmacokinetic parameters revealing druggability of the synthesized hybrids.

Design and synthesis of thiadiazolo-carboxamide bridged β-carboline-indole hybrids: DNA intercalative topo-IIα inhibition with promising antiproliferative activity

The conjoining of salient pharmacophoric properties directing the development of prominent cytotoxic agents was executed by constructing thiadiazolo-carboxamide bridged β-carboline-indole hybrids. On the evaluation of in vitro cytotoxic potential, 12c exhibited prodigious cytotoxicity among the synthesized new molecules 12a–k, with an IC50 50 value of 2.82 ± 0.10 μM. Besides, another compound 12a also displayed impressive cytotoxicity against A549 cell line (IC50: 3.00 ± 1.40 μM). Further target-based assay of these two compounds 12c and 12a revealed their potential as DNA intercalative topoisomerase-IIα inhibitors. Additionally, the antiproliferative activity of compound 12c was measured in A549 cells by traditional apoptosis assays revealing the nuclear, morphological alterations, and depolarization of membrane potential in mitochondria and externalization of phosphatidylserine in a concentration-dependent manner. Cell cycle analysis unveiled the G0/G1 phase inhibition and wound healing assay inferred the inhibition of in vitro cell migration by compound 12c in lung cancer cells. Remarkably, the safety profile of compound 12c was disclosed by screening against normal human lung epithelial cell line (BEAS-2B: IC50: 71.2 ± 7.95 μM) with a selectivity index range of 14.9–25.26. Moreover, Molecular modeling studies affirm the intercalative binding of compound 12c and 12a in the active pocket of topo-IIα. Furthermore, in silico prediction of physico-chemical parameters divulged the propitious drug-like properties of the synthesized derivatives.

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.

A practical synthesis of β-carbolines by tetra-n-butylammonium bromide (TBAB)-mediated cycloaromatization reaction of aldehydes with tryptophan derivatives

A mild and efficient nBu4NBr-mediated oxidative cycloaromatization to prepare β-carbolines from readily available tryptophans and aldehydes is described. The reaction is practical and allows the synthesis of β-carbolines on gram-scale. Some of

A method for synthesis of β - carbolines (by machine translation)

The invention relates to a β - carbolines synthesis method, the method comprises the formula (1) compound of formula (2) of the bromine compound in the catalyst [...], peroxide and organic solvent under the action of the [...] (3) compound, its general fo

Synthesis of podophyllotoxin linked β-carboline congeners as potential anticancer agents and DNA topoisomerase II inhibitors

A series of new podophyllotoxin linked β-carboline congeners have been synthesized by coupling various substituted β-carboline acids with 4β-aminopodophyllotoxin. Evaluation of their anticancer activity against a panel of human cancer cell lines such as lung cancer (A549), prostate cancer (DU-145), MDA MB-231 (breast cancer), HT-29 (colon cancer) and HeLa (cervical cancer) suggested that 7i and 7j are the most cytotoxic compounds with IC50 values of 1.07 ± 0.07 μM and 1.14 ± 0.16 respectively against DU-145 cell line. Further, detailed biological studies such as cell cycle analysis, topoisomerase II inhibition, Comet assay, DNA binding studies and docking studies have revealed that these congeners are DNA interacting topoisomerase II inhibitors.