85029-91-0Relevant academic research and scientific papers
An indicator displacement system for fluorescent detection of phosphate oxyanions under physiological conditions
Hanshaw, Roger G.,Hilkert, Sarah M.,Jiang, Hua,Smith, Bradley D.
, p. 8721 - 8724 (2004)
A fluorogenic chemosensing system is described and shown to selectively detect pyrophosphate under physiological conditions. In the best case, pyrophosphate and hydrogen phosphate are capable of displacing a fluorescent coumarin-derived indicator from a bis Zn2+-dipicolylamine coordination compound with association constants of 107 and 10 5 M-1, respectively.
Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment
Xia, Yang-Liu,Wang, Jing-Jing,Li, Shi-Yang,Liu, Yong,Gonzalez, Frank J.,Wang, Ping,Ge, Guang-Bo
, (2020/11/25)
Myeloid cell leukemia-1 (Mcl-1) is a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to their resistance to current chemotherapeutics. In this study, more than thirty coumarin derivatives with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. In addition, the introduction of a nitrogen-containing group to the C-5 or C-8 position, which allowed an intramolecular hydrogen bond, was also unfavorable for Mcl-1 inhibition. Among all coumarins tested, 4-trifluoromethyl-6,7-dihydroxycoumarin (Cpd 4) displayed the most potent inhibitory activity towards Mcl-1 (Ki = 0.21 ± 0.02 μM, IC50 = 1.21 ± 0.56 μM, respectively), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between Cpd 4 and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of Cpd 4. 3D-QSAR analysis of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. These findings could be of great value for medicinal chemists for the design and development of more potent Mcl-1 inhibitors for biomedical applications.
Coumarin-Caged Compounds of 1-Naphthaleneacetic Acid as Light-Responsive Controlled-Release Plant Root Stimulators
Han, Bao-Hang,Jarussophon, Suwatchai,Kaewchangwat, Narongpol,Niamnont, Nakorn,Prateepchinda, Sagaw,Suttisintong, Khomson,Thanayupong, Eknarin,Unger, Onuma,Yata, Teerapong
, p. 6268 - 6279 (2020/07/31)
Six coumarin-caged compounds of 1-naphthaleneacetic acid (NAA) comprising different substituents on the coumarin moiety were synthesized and evaluated for their photophysical and chemical properties as light-responsive controlled-release plant root stimulators. The 1H NMR and HPLC techniques were used to verify the release of NAA from the caged compounds. After irradiation at 365 nm, the caged compounds exhibited the fastest release rate at t1/2 of 6.7 days and the slowest release rate at t1/2 of 73.7 days. Caged compounds at high concentrations (10-5 and 10-6 M) significantly stimulate secondary root germination while free NAA at the same level is toxic and leads to inhibition of secondary root germination. The cytotoxicity of the caged compounds against fibroblasts and vero cells were evaluated, and the results suggested that, at 10-5-10-6 M, caged compounds exhibited no significant cytotoxicity to the cells. Thus, the caged compounds of NAA in this study could be of great benefit as efficient agrochemicals.
Theoretical and experimental investigation of NMR, IR and UV-visible spectra of hydroxyl-substituted-4-chloromethylcoumarin derivatives
Loarueng, Chutipapha,Boekfa, Bundet,Jarussophon, Suwatchai,Pongwan, Pawinee,Kaewchangwat, Narongpol,Suttisintong, Khomson,Jarussophon, Nongpanga
, p. 116 - 127 (2019/11/11)
UV-Visible, FTIR and NMR experimental and theoretical spectral results have been compared for five substituted-4-chloromethylcoumarin derivatives (6-OH, 7-OH, 6,7-di-OH, 7,8-di-OH and 5,7-di-OH-substituted-4-chloromethylcoumarins). The theoretical investigation was conducted using density functional theory (DFT), namely the M06-2X functional form with 6-311+G(2df,2p) basis set. The 13C-NMR and 1H-NMR chemical shifts, vibrational spectra and molecular orbitals of the excited states were calculated based on their optimized geometries. The calculated values were found to have close agreement with the experimental values. The theoretical data are useful and could be important in the proper selection of compounds as intermediates for different chemical applications and modifications.
Synthesis of 4-aryl-1,2,3-triazolyl appended natural coumarin-related compounds with antiproliferative and radical scavenging activities and intracellular ROS production modification
Bistrovi?,Stipani?ev,Opa?ak-Bernardi,Juki?,Martinez,Glava?-Obrovac, Lj,Rai?-Mali?
, p. 7531 - 7543 (2017/08/02)
Novel natural coumarin-based umbelliferone, herniarin and esculetin series linked to hydroxy- and methoxy-substituted and non-substituted phenyl rings through a 1,2,3-triazole spacer were provided by environmentally friendly click chemistry under microwave irradiation. The antioxidative activity of the compounds was evaluated by DPPH-scavenging activity and cyclic voltammetry assays. While adjacent 6- and 7-hydroxyl groups in coumarins made a major contribution to antioxidative power and a decrease of ROS production relative to esculetin, a p-methoxy-substituted phenyl moiety had an impact on pronounced and selective antiproliferative activity against chronic leukemia cells in blast crisis (K562) with no significant change in the ROS generation. 6,7-Dihydroxycoumarin can be considered as a promising scaffold with a major contribution to antioxidant potential and, thereby, further structural modification of 6,7-dihydroxycoumarin linked to aryl-1,2,3-triazole may provide a hybrid molecule that may be of interest for potential application to prevent diseases related to the oxidative-stress imbalance.
Design, synthesis and biological evaluation of esculetin derivatives as anti-tumour agents
Wang,Xia,Yu, Yang,Lu, Jun-Xia,Zou, Li-Wei,Feng, Lei,Ge, Guang-Bo,Yang, Ling
, p. 53477 - 53483 (2015/06/30)
Esculetin, a naturally catecholic coumarin, possess multiple pharmacological activities including anti-tumour, anti-inflammatory and anti-oxidant. However, the extensive phase II metabolism and rapid elimination from the human body significantly hinder esculetin and its derivatives as drug leads/candidates. To improve both the metabolic stability and the anti-tumour activity of esculetin via rational modification, a series of C-4 and C-8 substituted derivatives were designed and synthesized by perchloric acid catalysed von Pechmann reaction and Mannich reaction, respectively. The in vitro metabolic half-life in human liver S9 and anti-tumour activities in A549 and B16 cell lines of the newly synthesized compounds were assayed. Of these compounds, 8-(pyrrolidin-1-ylmethyl)-4-trifluoromethyl esculetin 15 was the most potent candidate compound, with almost a 20-fold increase in antiproliferative activity and a 3-fold prolonged half-life in human liver S9 compared with the parent compound 1. In addition, the potential structure-activity relationship and structure-metabolic stability relationship were discussed. Notably, the introduction of a nitrogen containing group as a hydrogen bond acceptor at the C-8 position of esculetin can improve both the metabolic stability and anti-tumour activity. All of these findings are very helpful for the structural modification of esculetin and other bioactive phenolic compounds to improve their phase II metabolic stability and bioactivity synchronously.
Synthesis, antielastase, antioxidant and radical scavenging activities of 4-(aza substituted) methylene substituted dihydroxy coumarines
Sokmen, Bahar Bilgin,Aydin, Gulsah,Gumus, Arzu,Karadeniz, Seref,Ugras, Halil Ibrahim,Yanardag, Refiye,Cakir, Umit
, p. 870 - 875 (2013/07/26)
A series of some 4-(aza substituted) methylene substituted dihydroxy coumarines were evaluated for their antioxidant and antielastase activities. Different in vitro methodologies such as total reducing power, 1,1-diphenyl-2-picryl-hydrazil (DPPH·) free radical scavenging, ABTS radical scavenging activity were used as antioxidant activity. All the tested compounds exhibited potent free radical scavenging ability and antielastase activites.
