244-63-3Relevant academic research and scientific papers
N2,N9-Bis(Substituted benzyl)-β-Carbolineum Bromides as Potential Anticancer Therapeutics: Design, Synthesis, Cytotoxicity, Drug-DNA Intercalation and In-Silico Binding Properties
Hamali, Muhamad Azwan,Kamaruzaman, Nur Azzalia,Mansor, Sharif Mahsufi,Mohideen, Mazlin,Mordi, Mohd Nizam,Rahman, A. F. M. Motiur
, (2021)
The present study reports a series of novel N2,N9-bis(substituted benzyl)-β-carbolineum bromides (4a-f) synthesized from L-tryptophan in three steps with excellent yields (>80%). The structures of synthesized compounds 4a-f were confirmed by 1H- and 13C-NMR, FT-IR, LC-MS (ESI-MS) spectrum and elemental analysis. Meanwhile, the crystal structure for compound 4f was determined by X-ray single-crystal diffraction. The crystal belongs in monoclinic space group in P121/c1 space group with a = 13.253(6) ?, b = 20.809(10) ?, c = 9.116(6) ?, β = 107.215(13)°, V = 2401.4(19) ?3 and Z = 4, F(000) = 1048, Dc = 1.403 Mg/m3 and μ = 1.743 mm?1. Compounds 4a-f were evaluated for their in-vitro anticancer activity against selected human cancer cell lines, such as HT-29 (colorectal adenocarcinoma), HeLa (cervical carcinoma), HepG2 (hepatocellular carcinoma) and K562 (chronic myelogenous leukaemia, CML). Results showed that compounds 4a-f exerted excellent cytotoxicity effect with IC50 values ranging from 0.36-1.08 μM against K562 human CML cell line. It was found that synthesized β-carbolines are much less toxic towards non-cancer cell lines BALB/c3T3 and Hs-27, in comparison to cisplatin and doxorubicin, which were employed as positive controls. To investigate the binding mode of these compounds against DNA, spectroscopic studies were conducted. Subsequent UV-Visible and in-silico (molecular docking) studies revealed that compound 4f interacts with DNA through intercalation. Based on the present findings, it was suggested that compound 4f has a great potential to be developed as a novel anticancer agent.
Naturally-occurring tetrahydro-β-carboline alkaloids derived from tryptophan are oxidized to bioactive β-carboline alkaloids by heme peroxidases
Herraiz, Tomás,Galisteo, Juan
, p. 42 - 47 (2014)
β-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-β-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-β-carbolines (i.e. 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) into aromatic β-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (VMAX and KM). Oxidation of tetrahydro-β-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H2O 2. The formation of aromatic β-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems.
Preparation and a novel rearrangement reaction of 1,2,3,4-tetrahydro-9- hydroxy-β-carboline, and their applications for the total synthesis of (±)- coerulescine
Somei,Noguchi,Yamagami,Kawada,Yamada,Yamada
, p. 7 - 10 (2000)
Novel 9-hydroxy-β-carboline derivatives were produced for the first time. A novel rearrangement reaction of 1,2,3,4-tetrahydro-9-hydroxy-β- carbolines was discovered to give 3,3-disubstituted oxindoles, which was successfully applied to the total synthesis of (±)-coerulescine.
Effect of the position of nitrogen in pyridoindole on photophysical properties and device performances of α-, β-, γ-carboline based high triplet energy host materials for deep blue devices
Im, Yirang,Lee, Jun Yeob
, p. 5948 - 5950 (2013)
Three carboline derivatives with nitrogen at different positions of the pyridoindole unit were synthesized and the effect of the position of nitrogen on the photophysical properties and device performances was investigated. β-Carboline was effective in obtaining high triplet energy and stabilizing energy levels, while α-carboline was better than other carbolines in terms of quantum efficiency. However, γ-carboline could not stabilize the LUMO level and low quantum efficiency was obtained.
Synthesis method of 9H-pyrido [3, 4-b] indole
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Paragraph 0027-0050, (2021/11/03)
The invention discloses a synthesis method of 9H-pyrido [3, 4-b] indole. The method comprises the following steps: taking tryptophan and chloroform as basic reaction raw materials, taking ferric salt as a catalyst, then adding alkali, carrying out cyclization aromatization reaction through free radical series connection, and finally carrying out post-treatment to obtain the 9H-pyrido [3, 4-b] indole product. According to the method, only commercially available tryptophan is used as a substrate, chloroform is used as a C1 source, a reaction precursor does not need to be prepared in advance, [5 + 1] cyclization aromatization is realized in a free radical series connection mode; and after C-C bond and C-N bond construction as well as decarboxylic acid and dehydrogenation aromatization process, without prior modification, addition of oxidizer, pre-preparation and separation of tetrahydrocarboline compounds, direct construction of pyridine heterocyclic slices can be realized througha one-pot method.
Visible light mediated selective oxidation of alcohols and oxidative dehydrogenation of N-heterocycles using scalable and reusable La-doped NiWO4nanoparticles
Abinaya, R.,Balasubramaniam, K. K.,Baskar, B.,Divya, P.,Mani Rahulan, K.,Rahman, Abdul,Sridhar, R.,Srinath, S.
, p. 5990 - 6007 (2021/08/24)
Visible light-mediated selective and efficient oxidation of various primary/secondary benzyl alcohols to aldehydes/ketones and oxidative dehydrogenation (ODH) of partially saturated heterocycles using a scalable and reusable heterogeneous photoredox catalyst in aqueous medium are described. A systematic study led to a selective synthesis of aldehydes under an argon atmosphere while the ODH of partially saturated heterocycles under an oxygen atmosphere resulted in very good to excellent yields. The methodology is atom economical and exhibits excellent tolerance towards various functional groups, and broad substrate scope. Furthermore, a one-pot procedure was developed for the sequential oxidation of benzyl alcohols and heteroaryl carbinols followed by the Pictet-Spengler cyclization and then aromatization to obtain the β-carbolines in high isolated yields. This methodology was found to be suitable for scale up and reusability. To the best of our knowledge, this is the first report on the oxidation of structurally diverse aryl carbinols and ODH of partially saturated N-heterocycles using a recyclable and heterogeneous photoredox catalyst under environmentally friendly conditions.
A convenient synthesis of β-carbolines by iron-catalyzed aerobic decarboxylative/dehydrogenative aromatization of tetrahydro-β-carbolines under air
Mohamad Arshad, Ahmad Saifuddin,Meesala, Ramu,Hanapi, Nur Aziah,Mordi, Mohd Nizam
, (2021/02/12)
A convenient synthesis for the conversion of various substituted tetrahydro-β-carbolines has been developed by iron-catalyzed decarboxylative/dehydrogenative aromatization to construct aromatic β-carbolines under air atmosphere. In the presence of a FeCl3 catalyst, this reaction exhibited a good functional group tolerance to produce corresponding β-carbolines in good yields in the absence of any additive. Additionally, the utility of the method was highlighted in the gram-scale synthesis of important natural β-carboline synthons norharmane (2a) and harmane (2b), which the latter provide practical access towards eudistomin N and nostocarboline.
TRICYCLIC CRBN LIGANDS AND USES THEREOF
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Paragraph 0750; 0753; 0754, (2020/01/24)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
Reusable, homogeneous water soluble photoredox catalyzed oxidative dehydrogenation of N-heterocycles in a biphasic system: Application to the synthesis of biologically active natural products
Abinaya, R.,Baskar, B.,Mariappan, M.,Prasanth, Arun,Sridhar, R.,Srinath, S.
, p. 2575 - 2587 (2020/05/13)
Herein, a simple and efficient method for the oxidative dehydrogenation (ODH) of tetrahydro-β-carbolines, indolines and tetrahydro-(iso)quinolines is described using a reusable, homogeneous cobalt-phthalocyanine photoredox catalyst in a biphasic medium. A biphasic system offers an advantage of easy separation of the product and an efficient reusability of the homogeneous photoredox catalyst. Also, the current system significantly helps to overcome the solubility issue of the substrate and catalyst at room temperature. Its potential applications to organic transformations are demonstrated by the synthesis of various biologically active N-heterocycles such as indoles, (iso)quinolines and β-carbolines and natural products such as eudistomin U, norharmane, and harmane and precursors to perlolyrine and flazin. Without isolation and purification, the catalyst solution can be reused up to 5 times with almost comparable reactivity. Furthermore, the efficiency of the reaction was demonstrated on a gram scale. To the best of our knowledge, this is the first report on ODH reactions using a non noble, reusable and homogeneous cobalt photoredox catalyst under environmentally friendly conditions.
Simultaneous generation of acrylamide, β-carboline heterocyclic amines and advanced glycation ends products in an aqueous Maillard reaction model system
Chen, Jie,He, Zhiyong,Jiao, Ye,Li, Yong,Liu, Guoping,Qin, Fang,Quan, Wei,Wang, Zhaojun,Xue, Chaoyi,Zeng, Maomao
, (2020/07/06)
The simultaneous formation of acrylamide; β-carboline heterocyclic amines (HAs): harmane and norharmane; and advanced glycation end products (AGEs) (Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL)) was analyzed based on an aqueous model system. The model systems included lysine–glucose (Lys/Glu), asparagine–glucose (Asn/Glu), tryptophan–glucose (Trp/Glu), and a mixture of these amino acids (Mix/Glu). Only AGEs were generated when heated at 100 °C, Asn and Trp competed with Lys for glucose and methylglyoxal (MGO), and glyoxal (GO) decreased AGE content. The k value of CML, CEL, and acrylamide decreased when heated at 130 °C, whereas that of harmane increased in the Mix/Glu, owing to the competition between Lys and Asn for glucose, GO, and MGO. Harmane preferably formed via the Pictet–Spengler condensation between Trp and acetaldehyde, which further reduced acrylamide formation via the acrolein pathway.
