6174-86-3Relevant articles and documents
2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases
Fernández-Bola?os, José G.,Fernandes, Miguel X.,Fuentes-Aguilar, Alma,López, óscar,Merino-Montiel, Penélope,Meza-Reyes, Socorro,Montiel-Smith, Sara,Nocentini, Alessio,Padrón, José M.,Petreni, Andrea,Puerta, Adrián,Supuran, Claudiu T.,Vega-Báez, José Luis
, p. 168 - 177 (2021/12/21)
We have carried out the design, synthesis, and evaluation of a small library of 2-aminobenzoxazole-appended coumarins as novel inhibitors of tumour-related CAs IX and XII. Substituents on C-3 and/or C-4 positions of the coumarin scaffold, and on the benzoxazole moiety, together with the length of the linker connecting both units were modified to obtain useful structure-activity relationships. CA inhibition studies revealed a good selectivity towards tumour-associated CAs IX and XII (K i within the mid-nanomolar range in most of the cases) in comparison with CAs I, II, IV, and VII (K i > 10 μM); CA IX was found to be slightly more sensitive towards structural changes. Docking calculations suggested that the coumarin scaffold might act as a prodrug, binding to the CAs in its hydrolysed form, which is in turn obtained due to the esterase activity of CAs. An increase of the tether length and of the substituents steric hindrance was found to be detrimental to in?vitro antiproliferative activities. Incorporation of a chlorine atom on C-3 of the coumarin moiety achieved the strongest antiproliferative agent, with activities within the low micromolar range for the panel of tumour cell lines tested.
A Copper Halide Promoted Regioselective Halogenation of Coumarins Using N-Halosuccinimide as Halide Source
Su, Jinling,Zhang, Yan,Chen, Mingren,Li, Weiming,Qin, Xuewei,Xie, Yanping,Qin, Lixiao,Huang, Shihua,Zhang, Min
supporting information, p. 630 - 634 (2019/03/08)
A safe, convenient, and regioselective synthesis of 3-halo coumarins using a metal halide (CuX 2 alone or with ZnX 2) promoted halogenation with N -halosuccinimide (NXS) as halide source is reported. The synthesis involved the steady in situ generation of highly reactive positive halogen (X +) by the coordination of copper or zinc with the N -halosuccinimide and subsequent electrophilic aromatic substitution of the electron-deficient coumarins. This procedure works well also for the halogenation of less electron-rich naphthoquinones, flavones, and methoxypsoralen in moderate to quantitative yields. This protocol features simple experimental conditions using readily available inexpensive reagents and provides a convenient approach to the chlorination or bromination of some useful heteroaromatic compounds.
Diethyl phosphite production from phosphorothioate degradation with molybdenum peroxides and hydrogen peroxide in ethanol
Kuo, Louis Y.,Miao, Qianli,Bright, Emily,Inoue, Kei,Phillips, Owen,Seaman, Joe,Ng, Megan,Kang, Lauren
supporting information, p. 229 - 234 (2018/09/05)
A polystyrene-supported molybdate-peroxide polymer (Mo-Y(s)) destroys phosphorothioate pesticides of the form (ArO)P(=S)(OEt)2 in EtOH under mild oxidative (H2O2) conditions and produces a commodity organophosphate. This is the first report of a metal-based system that successfully degrades the “live” pesticides parathion, diazinon and coumaphos. In addition to the operational advantages of heterogeneous reaction chemistry, the Mo-Y(s) support degrades multiple equivalents of the pesticide in H2O2(aq). Of particular importance is the predominant production of diethyl phosphite, a commodity chemical, from diazinon degradation over Mo-Y(s) in EtOH; no toxic oxon is found. Coumaphos and parathion produce the corresponding oxon which have ΔH? (kcal/mol) of 15.4 (0.5) and 21.7 (0.8), respectively; these activation parameters are consistent with key observations found in the relative amount of coumoxon and paraoxon produced. Finally, a discrete molybdate-peroxide complex is presented as a possible solution model for this heterogeneous reaction.
Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
Yu, Haonan,Hou, Zhuang,Tian, Ye,Mou, Yanhua,Guo, Chun
, p. 434 - 449 (2018/04/14)
To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.
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, characterization and biological approach of metal chelates of some first row transition metal ions with halogenated bidentate coumarin Schiff bases containing N and O donor atoms
Prabhakara, Chetan T.,Patil, Sangamesh A.,Toragalmath, Shivakumar S.,Kinnal, Shivashankar M.,Badami, Prema S.
, p. 1 - 14 (2016/04/04)
The impregnation of halogen atoms in a molecule is an emerging trend in pharmaceutical chemistry. The presence of halogens (Cl, Br, I and F) increases the lipophilic nature of molecule and improves the penetration of lipid membrane. The presence of electronegative halogen atoms increases the bio- activity of core moiety. In the present study, Co(II), Ni(II) and Cu(II) complexes are synthesised using Schiff bases (HLI and HLII), derived from 8-formyl-7-hydroxy-4-methylcoumarin/3-chloro-8-formyl-7-hydroxy-4-methylcoumarin with 2,4-difluoroaniline/o-toluidine respectively. The synthesized compounds were characterized by spectral (IR, NMR, UV-visible, Mass, ESI-MS, ESR), thermal, fluorescence and molar conductivity studies. All the synthesized metal complexes are completely soluble in DMF and DMSO. The non-electrolytic nature of the metal complexes was confirmed by molar conductance studies. Elemental analysis study suggest [ML2(H2O)2] stoichiometry, here M = Co(II), Ni(II) and Cu(II), L = deprotonated ligand. The obtained IR data supports the binding of metal ion to Schiff base. Thermal study suggests the presence of coordinated water molecules. Electronic spectral results reveal six coordinated geometry for the synthesized metal complexes. The Schiff bases and their metal complexes were evaluated for antibacterial (Pseudomonas aureginosa and Proteus mirabilis), antifungal (Aspergillus niger and Rhizopus oryzae), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activities.
Design, synthesis and cytotoxicity of novel dihydroartemisinin-coumarin hybrids via click chemistry
Tian, Ye,Liang, Zhen,Xu, Hang,Mou, Yanhua,Guo, Chun
, (2016/07/07)
In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05-125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a - e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.
Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
Xie, Sai-Sai,Wang, Xiaobing,Jiang, Neng,Yu, Wenying,Wang, Kelvin D.G.,Lan, Jin-Shuai,Li, Zhong-Rui,Kong, Ling-Yi
supporting information, p. 153 - 165 (2015/03/31)
A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 11/4M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment.
Flow microwave technology and microreactors in synthesis
Baxendale, Ian R.,Hornung, Christian,Ley, Steven V.,De Mata Munoz Molina, Juan,Wikstroem, Anders
, p. 131 - 144 (2013/03/28)
A bespoke microwave reactor with a glass containment cell has been developed for performing continuous flow reactions under microwave heating. The prototype unit has been evaluated using a series of standard organic chemical transformations enabling scale-up of these chemical processes. As part of the development, a carbon-doped PTFE reactor insert was utilized to allow the heating of poorly absorbing reaction media, increasing the range of solvents and scope of reactions that can be performed in the device.
Establishing a flow process to coumarin-8-carbaldehydes as important synthetic scaffolds
Zak, Jaroslav,Ron, David,Riva, Elena,Harding, Heather P.,Cross, Benedict C. S.,Baxendale, Ian R.
supporting information; experimental part, p. 9901 - 9910 (2012/09/07)
Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8-carbaldehydes are lacking. We describe here a high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up, giving access to multigram quantities of the aldehyde product. Aldehyde on tap: Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8- carbaldehydes are lacking. A high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up is described, giving access to multigram quantities of aldehyde product (see scheme). Copyright
