2973-76-4Relevant academic research and scientific papers
Synthesis and biological evaluation of novel N,N′-bis- methylenedioxybenzyl-alkylenediamines as bivalent anti-Alzheimer disease ligands
Luo, Wen,Li, Yan-Ping,Tan, Jia-Heng,Gu, Lian-Quan,Huang, Zhi-Shu
, p. 706 - 711 (2011)
A novel series of N,N′-bis-methylenedioxybenzyl-alkylenediamines 5a5g have been designed, synthesized and evaluated as bivalent anti-Alzheimer's disease ligands. The enzyme inhibition assay results indicated that compounds 5e5g inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the micromolar range (IC50, 2.764.24 M for AChE and 3.025.14 M for BuChE), which was in the same potential as the reference compound rivastigmine (IC50, 5.50 M for AChE and 1.60 M for BuChE). It was found that compounds could bind simultaneously to the peripheral and catalytic sites of AChE. β-Amyloid (Aβ) aggregation inhibition assay results showed that compound 5e exhibited highest self-mediated Aβ fibril aggregation inhibition activity (40.3%) with a similar potential as curcumin (41.6%). It was also found that 5e5g did not affect neuroblastoma cell viability at the concentration of 50 μM.
Synthesis of the Sesquiterpenes Albicanol, Drimanol, and Drimanic Acid, and the Marine Sesquiterpene Hydroquinone Deoxyspongiaquinol
G?hl, Matthias,Seifert, Karlheinz
, p. 6975 - 6982 (2014)
A TiIII-mediated radical cyclization cascade has been used for the synthesis of the sesquiterpenes (+)-albicanol, (+)-drimanol, and (+)-drimanic acid. Starting from all-trans-farnesol, (+)-albicanol could be prepared in seven steps in an overal
Synthesis and Pharmacological Evaluation of Noscapine-Inspired 5-Substituted Tetrahydroisoquinolines as Cytotoxic Agents
Devine, Shane M.,Yong, Cassandra,Amenuvegbe, Dzifa,Aurelio, Luigi,Muthiah, Divya,Pouton, Colin,Callaghan, Richard,Capuano, Ben,Scammells, Peter J.
, p. 8444 - 8456 (2018)
A series of 5-substituted tetrahydroisoquinolines was synthesized via a 10-step linear synthesis to assess whether replacement of noscapine's southern isobenzofuranone with other moieties resulted in retained cytotoxic activity. One such molecule, 18g, bearing a para-methoxybenzyl functionality with N-ethylcarbamoyl substitution, produced cell-cycle arrest at the G2/M phase with an EC50 of 2.7 μM in the MCF-7 breast-cancer cell line, a 7-fold increase compared with that of noscapine (5). This molecule had similar activity (EC50 of 2.5 μM) against the resistant NCI/AdrRES cell line, demonstrating its potential to overcome or avert known resistance mechanisms, unlike current cytotoxic agents. Compound 18g was found to modify the drug-efflux activity of P-gp and, in combination studies, potentiate the antiproliferative activity of vinblastine. These results provide insights into structural modifications to noscapine that will guide future development toward more potent cytotoxic agents that are active against resistant cancer cells.
Syntheses of novel pyrazolines as antibacterial agents from natural product vanillin
Setyawati, Amri,Wahyuningsih, Tutik Dwi,Purwono, Bambang
, p. 454 - 456 (2017)
A series of pyrazoline derivatives have been synthesized from natural vanillin and tested as antibacterial agents by diffusion method. Pyrazolines were synthesized from vanillin via chalcone intermediate. The structure of all the products was elucidated b
Design, synthesis and biochemical evaluation of novel 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid using Horseradish peroxidase (HRP) activity, cellular ROS inhibition and molecular docking study
Demonceau, Albert,Etsè, Koffi Sénam,Mouithys-Mickalad, Ange,Serteyn, Didier,Zaragoza, Guillermo
, (2021/10/29)
In this paper, we report the design, synthesis and biochemical evaluation of 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid 9, a myristicin derivative, from cheap and available vanillin as starting material. Compound 9 is identified as a potential precursor of natural brasiliamide derivatives. All the products are fully characterized. The crystal structure of the intermediate diethyl 2-acetamido-2-((7-methoxybenzo[d][1,3]dioxol-5-yl)methyl)malonate 16, a precursor of this amino acid, is obtained and presented. The interactions stabilizing the crystal packing of 16 were deeply analyzed by considering first the supramolecular stacking and finally, by analyzing the contacts descriptors on the Hirshfeld surface, the molecular fingerprint and the intermolecular energy. Different biochemical properties of the desired amino acid 9 and its selected precursors are investigated. In DPPH test, 9 showed the best anti-radical activity (IC50 = 80.91 μM). The enzymatic, HRP-H2O2/L012, chemiluminescence assay reveals excellent inhibitory effect on the peroxidase activity and a good antioxidant activity of all the tested compounds with the best activity for 9 (IC50 = 0.36 μM). The anti-peroxidase activity observed for compound 9 was confirmed by molecular docking exploration that allows to identify interactions in the HRP-9 complex. Docking results showed that 9 interacts with catalytic and active site residues, especially with Arg38, His42, Ser73, Phe68 and Pro139. Moreover, the inhibition of ROS production by activated HL-60 cells was moderately obtained with compounds 9 and 13. The MTS cell viability test reveals that all tested compounds, except myristicin aldehyde 13, were not cytotoxic indicating that the observed inhibition of ROS production of activated HL-60 cells was not due to cells death. Finally, physicochemical and ADME-Tox predictions suggested that compound 9 could be considered as promising drug candidate.
First synthesis of tabamides A–C and their derivatives: In vitro nitric oxide inhibitory activity
Damodar, Kongara,Shin, Sooyong,Jeon, Sung Ho,Lee, Jeong Tae
supporting information, (2021/11/10)
The first synthesis of natural phenolic amides, tabamides A–C (1–3), and their derivatives (4–12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 μM), followed by tabamide A (1, IC50 = 100.7 μM), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents.
Antidiabetic activity in vitro and in vivo of BDB, a selective inhibitor of protein tyrosine phosphatase 1B, from Rhodomela confervoides
Guo, Shuju,Jiang, Bo,Li, Chao,Li, Xiangqian,Luo, Jiao,Shi, Dayong,Wang, Lijun,Yu, Rilei,Zheng, Meiling
, (2020/09/02)
Background and Purpose: Protein tyrosine phosphatase (PTP) 1B (PTP1B) plays a critical role in the regulation of obesity, Type 2 diabetes mellitus and other metabolic diseases. However, drug candidates exhibiting PTP1B selectivity and oral bioavailability are currently lacking. Here, the enzyme inhibitory characteristics and pharmacological benefits of 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) were investigated in vitro and in vivo. Experimental Approach: Surface plasmon resonance (SPR) assay was performed to validate the direct binding of BDB to PTP1B, and Lineweaver–Burk analysis of the enzyme kinetics was used to characterise the inhibition by BDB. Both in vitro enzyme-inhibition assays and SPR experiments were also conducted to study the selectivity exhibited by BDB towards four other PTP-family proteins: TC-PTP, SHP-1, SHP-2, and LAR. C2C12 myotubes were used to evaluate cellular permeability to BDB. Effects of BDB on insulin signalling, hypoglycaemia and hypolipidaemia were investigated in diabetic BKS db mice, after oral gavage. The beneficial effects of BDB on pancreatic islets were examined based on insulin and/or glucagon staining. Key Results: BDB acted as a competitive inhibitor of PTP1B and demonstrated high selectivity for PTP1B among the tested PTP-family proteins. Moreover, BDB was cell-permeable and enhanced insulin signalling in C2C12 myotubes. Lastly, oral administration of BDB produced effective antidiabetic effects in spontaneously diabetic mice and markedly improved islet architecture, which was coupled with an increase in the ratio of β-cells to α-cells. Conclusion and Implications: BDB application offers a potentially practical pharmacological approach for treating Type 2 diabetes mellitus by selectively inhibiting PTP1B.
Bromophenol-pyrazoline compound as well as synthesis method and application thereof (by machine translation)
-
Paragraph 0026-0029, (2020/11/12)
The invention relates to a compound, in particular to a bromophenol-pyrazoline compound as well as a synthesis method and application thereof. The bromophenol-pyrazoline compound has the following structural general formula: The bromophenol-pyrazoline compound provided by the invention has high-efficiency main protease MPro Activity can be inhibited, and the replication of coronavirus can be disturbed in cells, so that the compound has the efficacy of treating coronavirus pneumonia, and has wide application prospects in preparation of medicines for treating coronavirus pneumonia. (by machine translation)
Stepwise mechanism for the bromination of arenes by a hypervalent iodine reagent
Arrieta, Ana,Cossío, Fernando P.,Granados, Albert,Shafir, Alexandr,Vallribera, Adelina
, p. 2142 - 2150 (2020/03/11)
A mild, metal-free bromination method of arenes has been developed using the combination of bis(trifluoroacetoxy)iodobencene and trimethylsilyl bromide. In situ-formed dibromo(phenyl)-λ3-iodane (PhIBr2) is proposed as the reactive intermediate. This methodology using PIFA/TMSBr has been applied with success to a great number of substrates (25 examples). The treatment of mono-substituted activated arenes led to para-brominated products (2u-z) in excellent 83-96% yields. Density functional theory calculations indicate a stepwise mechanism involving a double bromine addition followed by a type II dyotropic reaction with concomitant re-aromatization of the six-membered ring.
Design, synthesis, and activity evaluation of novel N-benzyl deoxynojirimycin derivatives for use as α-glucosidase inhibitors
Zeng, Fanxin,Yin, Zhongping,Chen, Jiguang,Nie, Xuliang,Lin, Ping,Lu, Tao,Wang, Meng,Peng, Dayong
, (2019/09/19)
To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyldeoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NBDNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1- (4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5- methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α- glucosidase. Additionally, an arene-arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene-arene interaction resulted in a low binding energy (-5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type II diabetes.
