83688-44-2Relevant academic research and scientific papers
Modified coumarins. 12. Synthesis of 3,4-cycloannelated coumarin β-d-glucopyranosides
Garazd,Garazd,Khilya
, p. 6 - 12 (2004)
O-β-D-Glucopyranosides were synthesized using 3,4-cycloannelated hydroxycoumarins as aglycons. Phenolic hydroxyls were O-glycosylated via condensation of coumarin potassium salts with acetobromoglucose in homogeneous medium and in a liquid-liquid system using a phase-transfer catalyst.
Tricyclic coumarin sulphonate derivatives with alkaline phosphatase inhibitory effects: in vitro and docking studies
Iqbal, Jamshed,El-Gamal, Mohammed I.,Ejaz, Syeda Abida,Lecka, Joanna,Sévigny, Jean,Oh, Chang-Hyun
, p. 479 - 484 (2018/02/14)
Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC50 = 0.38 ± 0.01 μM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC50 = 0.45 ± 0.02 μM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes.
Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation
He, Qi,Liu, Jing,Lan, Jin-Shuai,Ding, Jiaoli,Sun, Yongbing,Fang, Yuanying,Jiang, Neng,Yang, Zunhua,Sun, Liyuan,Jin, Yi,Xie, Sai-Sai
supporting information, p. 512 - 528 (2018/09/29)
A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068 μM and 0.0089 μM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 μM for hAChE; 0.101 μM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
Synthesis of New Tricyclic and Tetracyclic Fused Coumarin Sulfonate Derivatives and Their Inhibitory Effects on LPS-Induced Nitric Oxide and PGE2 Productions in RAW 264.7 Macrophages: Part 2
El-Gamal, Mohammed I.,Lee, Woo-Seok,Shin, Ji-Sun,Oh, Chang-Hyun,Lee, Kyung-Tae,Choi, Jungseung,Myoung, Nohsun,Baek, Daejin
, p. 853 - 863 (2016/11/09)
The synthesis of a new series of 21 fused coumarin derivatives is described, and the biological evaluation of their in vitro antiinflammatory effects as inhibitors of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages. The target compounds 1a–u were first tested for cytotoxicity to determine a non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production would not be caused by cytotoxicity. Compounds 1f and 1p were the most active PGE2 inhibitors with IC50 values of 0.89 and 0.95 μM, respectively. Western blot and cell-free COX-2 screening showed that their effects were due to inhibition of both COX-2 protein expression and COX-2 enzyme activity. Their IC50 values against the COX-2 enzyme were 0.67 and 0.85 μM, respectively, which is more potent than etoricoxib. The selectivity indexes of compounds 1f and 1p against COX-2 compared to COX-1 were 41.1 and 42.5, respectively. Compound 1f showed strong inhibitory effects at 5 μM concentration on COX-2 mRNA expression in LPS-induced RAW 264.7 macrophages. Moreover, the tricyclic compounds 1l and 1n as well as the tetracyclic analog 1u were the most potent NO inhibitors, with one-digit micromolar IC50 values. They showed dose-dependent inhibition of inducible nitric oxide synthase (iNOS) protein expression. The tetracyclic derivative 1u was the most potent inhibitor of NO production. It also exhibited a strong inhibitory effect on iNOS mRNA expression in LPS-induced RAW 264.7 macrophages.
Synthesis of tricyclic fused coumarin sulfonates and their inhibitory effects on LPS-induced nitric oxide and PGE2 productions in RAW 264.7 macrophages
Jang, Hyeon-Lok,El-Gamal, Mohammed I.,Choi, Hye-Eun,Choi, Ho-Yeong,Lee, Kyung-Tae,Oh, Chang-Hyun
, p. 571 - 575 (2014/01/23)
The regulations of NO and PGE2 productions are research topics of interest in the field of antiinflammatory drug development. In the present study, a series of tricyclic fused coumarin sulfonate derivatives was synthesized and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 macrophages. Among all the target compounds, compound 1g possessing p-(trifluoromethyl)phenyl and fused cycloheptane moieties showed the highest inhibitory effects on NO and PGE 2 productions. Compound 1g not only inhibited COX-2 activity but also reduced expressions of COX-2 and iNOS. Furthermore, ADME profiling showed that compounds 1g, 1j, 1m, and 1n are estimated to be orally bioavailable.
Synthesis, in vitro antiproliferative activity, and in silico studies of fused tricyclic coumarin sulfonate derivatives
El-Gamal, Mohammed I.,Oh, Chang-Hyun
, p. 68 - 76 (2014/07/22)
A series of fused tricyclic coumarin sulfonate derivatives was synthesized. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 1e, 1f, 1h, 1i, and 1o showed the highest mean percentage of inhibition values over the 57 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values. Compounds 1e, 1f, and 1o were more selective against leukemia and colon cancer subpanels, while compounds 1h and 1i showed broad-spectrum anticancer activities. Compounds 1e, 1f, 1h, 1i, and 1o demonstrated high selectivity towards cancer cell lines than RAW 264.7 macrophages. Compound 1h exerted lethal effect over NCI-H522 NSCLC, SK-MEL-5 melanoma, and A498 renal cancer cell lines with percentage of inhibition values of 114.10%, 103.23%, and 100.52% at 10 μM concentration, respectively. Moreover, the IC50 value of compound 1o against HT29 colon cancer cell line was 532 nM. Compounds 1e, 1f, 1h, 1i, and 1o were tested for inhibitory effect over cyclooxygenase-2 (COX-2) enzyme as a possible mechanism of action. Furthermore, in silico studies were conducted to check the compliance of those five compounds with Lipinski's rule of five, and hence estimate their oral bioavailability.
Phosphate tricyclic coumarin analogs as steroid sulfatase inhibitors: Synthesis and biological activity
Kozak, Witold,Dasko, Mateusz,Maslyk, Maciej,Pieczykolan, Jerzy S.,Gielniewski, Bartlomiej,Rachon, Janusz,Demkowicz, Sebastian
, p. 44350 - 44358 (2014/12/10)
In the present work, we report convenient methods for the synthesis and biological evaluation of phosphate tricyclic coumarin derivatives as potential steroid sulfatase inhibitors. The described synthesis includes the straightforward preparation of 7-hydroxy-2,3-dihydro-1H-cyclopenta[c]chromen-4-one, 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-6-one modified with various phosphate moieties. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta as well as the MCF-7, MDA-MB-231 and MDA-MB-435S cancer cell lines. Most of the new STS inhibitors possessed IC50 values between 21 to 159 μM. In the course of our investigation, the largest inhibitory effects in the STS enzyme assays were observed for the three compounds 9p, 9r and 9s, with IC50 values of 36.4, 37.8 and 21.5 μM, respectively (IC50 value of 1.0 μM for the 665-COUMATE used as a reference). The compound 9r, exhibited the highest potency against MCF-7, an estrogen receptor positive (ER+) cell line, with a GI50 value of 24.7 μM. The structure-activity relationships of the synthesized coumarin derivatives with the STS enzyme are discussed.
SOLID PHARMACEUTICAL COMPOSITION CONTAINING 6-OXO-6,7,8,9,10,11-HEXAHYDROCYCLOHEPTA (C)CHROMEN-3-YL SULFAMATE AND POLYMORPHS THEREOF
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Page/Page column 12, (2013/02/27)
The present invention relates to a solid pharmaceutical composition including the active principle 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate. The present invention also relates to polymorphs of the 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate compound.
Modified coumarins. 24. Synthesis of cycloheptane-annellated tetracyclic furocoumarins
Garazd,Garazd,Ogorodniichuk,Khilya
, p. 656 - 664 (2008/02/09)
Substituted 2,3,4,5-tetrahydrocyclohepta[c]furo[3,2-g]chromen-6-ones, modified psoralen analogs containing a cycloheptane ring annellated to the 5,6-positions of a furo[3,2-g]chromen-7-one, were synthesized from 3-hydroxy-8,9,10,11-tetrahydrocyclohepta[c]
Skeletal diversity construction via a branching synthetic strategy
Wyatt, Emma E.,Fergus, Suzanne,Galloway, Warren R. J. D.,Bender, Andreas,Fox, David J.,Plowright, Alleyn T.,Jessiman, Alan S.,Welch, Martin,Spring, David R.
, p. 3296 - 3298 (2008/09/19)
A branching synthetic strategy was used to efficiently generate structurally diverse scaffolds, which span a broad area of chemical descriptor space, and their biological activity against MRSA was demonstrated. The Royal Society of Chemistry 2006.
