50302-61-9Relevant academic research and scientific papers
β-Carboline tethered cinnamoyl 2-aminobenzamides as class I selective HDAC inhibitors: Design, synthesis, biological activities and modelling studies
Godugu, Chandraiah,Kamal, ahmed,Lakshmi Manasa, Kesari,Namballa, Hari Krishna,Shankaraiah, Nagula,Soni, Jay Prakash,anchi, Pratibha
, (2021/11/11)
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.
Tetrahydro-beta-carboline dimer as well as preparation method and application thereof
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Paragraph 0075-0078, (2020/09/30)
The invention discloses an application of a tetrahydro-beta-carboline dimer derivative in the preparation of a medicine for preventing or treating Alzheimer's disease. The tetrahydro-beta-carboline dimer derivative is as shown in a structural formula I, which is described in the specification, L-tryptophan and tryptamine are used as raw materials; a tetrahydro-beta-carboline monomer is generated through a Picet-Spengler reaction and aldehyde cyclization, then a tetrahydro-beta-carboline dimer is generated through acyl chloride connection and a click chemical reaction, the synthesis steps are simple, the raw materials are easy to obtain, the yield is high, and the tetrahydro-beta-carboline dimer has remarkable inhibitory activity on butyrylcholine esterase and A[beta]1-42 aggregation. According to the neural protective effect under three AD models on cells, after the cells are independently treated by A[beta]1-42, H2O2 and OA, the survival rate of the cells is low, and apoptosis or necrosis of the cells occurs. The compounds 11, 12, 13, 17 and 19 are used for co-treatment, the compounds 11, 12, 13, 17 and 19 successfully block A[beta]1-42, H2O2 and OA induced cell death, and it is proved that the compounds 11, 12, 13, 17 and 19 have a remarkable neural protective effect.
Synthesis, Antileishmanial Activity and Spin Labeling EPR Studies of Novel β-Carboline-Oxazoline and β-Carboline-Dihydrooxazine Derivatives
Alonso, Antonio,Alonso, Laís,Baréa, Paula,Nakamura, Celso V.,Sarragiotto, Maria H.,da Costa, Willian F.,de Oliveira, Aline R.,de Paula, Jéssica C.
, p. 1170 - 1185 (2020/10/14)
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.
Bimetallic catalyzed N-arylation used in synthesis of novel β-carbolines derivatives
Cai, Rui,Wang, Pengfei,Zhao, Yu,Zhu, Li
, p. 520 - 525 (2020/04/17)
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
Cu-catalyzed mild and efficient oxidation of THβCs using air: Application in practical total syntheses of perlolyrine and flazin
Zheng, Bo,Trieu, Tien Ha,Meng, Tian-Zhuo,Lu, Xia,Dong, Jing,Zhang, Qiang,Shi, Xiao-Xin
, p. 6834 - 6839 (2018/02/23)
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.
Pd/C-Catalyzed Dehydrogenative [3+2] Cycloaddition for the Synthesis of Functionalized Tropanes
Wang, Hai-Jun,Guo, Lei,Zhu, Cheng-Feng,Luo, Yun-Fei,Li, You-Gui,Wu, Xiang
supporting information, p. 5456 - 5459 (2018/10/20)
A Pd/C-catalyzed cascade approach for the synthesis of attractive benzo-fused tropanes was developed. The reaction proceeds through a sequential Pd/C-catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3-dipolar cycloaddition. It allows the generation of structurally complex benzo-fused tropanes in good yields with excellent diastereoselectivities under mild reaction conditions. Preliminary results of asymmetric version of the reaction reveal that the copper catalyst and chiral monophosphoramidite ligand can furnish optically active products with moderate ee.
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
Kurumanna,Ashok,Rambabu,Sonyanaik,Ravi,Madhu,Sakram
, p. 2703 - 2711 (2017/12/26)
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.
A cephalotaxine with alkali compounds and in preventing the application of the litchi [...] mildew
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, (2017/10/07)
The present invention discloses a harmine compound, wherein the chemical structure formula is represented by a formula (I), R1 is selected from phenyl, p-nitrophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl, p-trifluoromethylphenyl and p-chlorophenyl, R2
Phytochemical meanings of tetrahydro-β-carboline moiety in strictosidine derivatives
Sud?ukovi?, Nicole,Schinnerl, Johann,Brecker, Lothar
supporting information, p. 588 - 595 (2016/02/09)
Synthesis of 13 different tetrahydro-β-carbolines (THBC) was accomplished by applying the Pictet-Spengler reaction with seven aldehydes, which have been coupled with tryptamine (6) and l-tryptophan methyl ester (7), respectively. The resulting products represent analogues of strictosidine (1) and carboxystrictosidine (5). They were investigated with respect to possible effects on herbivores in feeding bioassays upon the generalist Spodoptera littoralis. Maximum inhibition averages were 42% after four and 46% after six days for the most effective product (19) at 1000 ppm. Additionally, the frass of this particular bioassay was investigated via HPLC-UV for THBC digestion. All synthesized THBCs were also tested for their radical scavenger activity by monitoring their interaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 16-20, 24 and 25 exhibited radical scavenging activity, ranging from 50% to 74% compared to that of α-tocopherol. All results were discussed with respect to possible contributions of tetrahydro-β-carboline moieties in bioactivities of strictosidine (1) and its biodegradation products.
Convenient synthesis of 1-aryl-9H-β-carboline-3-carbaldehydes and their transformation into dihydropyrimidinone derivatives by Biginelli reaction
ábrányi-Balogh, Péter,Dancsó, András,Frigyes, Dávid,Volk, Balázs,Keglevich, Gy?rgy,Milen, Mátyás
, p. 5711 - 5719 (2015/03/30)
In the present work, a practical synthesis of 1-aryl-β-carboline-3-carbaldehydes as versatile building blocks and their application in Biginelli reaction is reported. The starting material of the four-step synthesis is racemic tryptophan methyl ester. The procedure involves a Pictet-Spengler cyclization, a dehydrogenation, an ester reduction, and an alcohol oxidation step. The β-carboline-3-carbaldehydes were further transformed using a Biginelli reaction into derivatives containing a pharmacologically significant dihydropyrimidine ring at position-3.
