400782-57-2

Upstream product

• 380895-65-8 1-(3-nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 
• 528524-76-7 methyl 1-(3-nitrophenyl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylate 
• 67-56-1 methanol 
• 99-61-6 3-nitro-benzaldehyde 
• 73-22-3 L-Tryptophan 
• 4299-70-1 L-tryptophan methyl ester 

Downstream Products

• 1085709-08-5 C₁₈H₁₃N₅O₃ 
• 1345667-67-5 N'-cyclohexylidene-1-(3-nitrophenyl)-β-carboline-3-carbohydrazide 
• 1345667-73-3 N'-cyclopentylidene-1-(3-nitrophenyl)-β-carboline-3-carbohydrazide 
• 1345667-81-3 N'-2-propylidene-1-(3-nitrophenyl)-β-carboline-3-carbohydrazide 
• 1345667-87-9 N'-(4-dimethylaminobenzylidene)-9-methyl-1-(3-nitrophenyl)-β-carboline-3-carbohydrazide 
• 1345667-59-5 C₂₅H₁₇N₅O₃ 

Relevant academic research and scientific papers

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.

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.

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, 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.

Dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acids and their esters with dimethyl sulfoxide

Oxidative dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylic acids derivatives with dimethyl sulfoxide leads to the formation of 1-aryl(hetaryl)-9Н-β-carbolines. Simultaneously with the dehydrogenation decarboxylation occurs

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.

Synthesis, in vitro antiproliferative and anti-mycobacterium tuberculosis activities of novel β-carboline derivatives

A series of β-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline (24.9 μg mL-1) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline (26.9 μg mL-1) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI50) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (27.8 μg mL-1) and 1-(3-nitrophenyl)-3-carboxamide(ethyl) guanidine β-carboline (37.4 μg mL-1) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (GI50 = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability.

Synthesis and antitumor activity of β-carboline 3-(substituted- carbohydrazide) derivatives

A series of β-carboline derivatives bearing a substituted- carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The b-carboline N-(substituted-benzylidene)carbohydrazides showed, i

Room-temperature aromatization of tetrahydro-β-carbolines by 2-iodoxybenzoic acid: Utility in a total synthesis of eudistomin U

2-Iodoxybenzoic acid is a convenient reagent for the dehydrogenation of tetrahydro-β-carbolines to their aromatic forms under mild conditions. The utility of the method was demonstrated in a total synthesis of the marine indole alkaloid eudistomin U.

Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)

Several novel 1,3-disubstituted β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity against both vaccinal poliovirus and HSV-1 virus. Compound 10 presented the highest selectivity index (SI = 2446.8) against HSV-1 virus and low cytotoxicity (CC50 = 1150.0 ± 67.3 μM). The virus yield inhibition assay showed that compound 10 was able to inhibit HSV-1 plaque formation before and during the virus adsorption. The characteristic small plaque pattern observed in compound-treated cells suggested that compound 10 inhibited viral dissemination to neighboring cells. A computational study for prediction of ADME properties of the novel synthesized β-carbolines derivatives was performed by determination of lipophilicity, topological polar surface area (TPSA), absorption (% ABS) and simple molecular descriptors, using Lipinski′s rule.