19088-73-4Relevant articles and documents
A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures
Deiana, Marco,Obi, Ikenna,Andreasson, M?ns,Tamilselvi, Shanmugam,Chand, Karam,Chorell, Erik,Sabouri, Nasim
, p. 1365 - 1376 (2021)
G-quadruplex (G4) DNA structures are widespread in the human genome and are implicated in biologically important processes such as telomere maintenance, gene regulation, and DNA replication. Guanine-rich sequences with potential to form G4 structures are prevalent in the promoter regions of oncogenes, and G4 sites are now considered as attractive targets for anticancer therapies. However, there are very few reports of small "druglike"optical G4 reporters that are easily accessible through one-step synthesis and that are capable of discriminating between different G4 topologies. Here, we present a small water-soluble light-up fluorescent probe that features a minimalistic amidinocoumarin-based molecular scaffold that selectively targets parallel G4 structures over antiparallel and non-G4 structures. We showed that this biocompatible ligand is able to selectively stabilize the G4 template resulting in slower DNA synthesis. By tracking individual DNA molecules, we demonstrated that the G4-stabilizing ligand perturbs DNA replication in cancer cells, resulting in decreased cell viability. Moreover, the fast-cellular entry of the probe enabled detection of nucleolar G4 structures in living cells. Finally, insights gained from the structure-activity relationships of the probe suggest the basis for the recognition of parallel G4s, opening up new avenues for the design of new biocompatible G4-specific small molecules for G4-driven theranostic applications.
Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals
Hu, Zhe-Yi,Li, Xiu-Xue,Du, Fei-Fei,Yang, Jun-Ling,Niu, Wei,Xu, Fang,Wang, Feng-Qing,Li, Chuan,Sun, Yan
, p. 1437 - 1448 (2013)
Aim: To investigate the pharmacokinetics and disposition of simmitecan (L-P) that was a water-soluble ester prodrug of chimmitecan (L-2-Z) with potent anti-tumor activities in different experimental animals, and to assess its drug-drug interaction potential. Methods: SD rats were injected with a single iv bolus doses of L-P (3.75, 7.5 and 15 mg/kg). The pharmacokinetics, tissue distribution, excretion and metabolism of L-P and its active metabolite L-2-Z were studied through quantitative measurements and metabolite profiling with LC/MS. The binding of L-P and L-2-Z to rat plasma proteins was examined using an ultrafiltration method. Systemic exposures of beagle dogs to L-P as well as drug distribution in tumors of the nude mice xenograft model of human hepatic cancer SMMC-7721 cells were also examined. The metabolism of L-P by liver mcirosomal carboxylesterase in vitro was investigated in different species. The effects of L-P and L-2-Z on cytochrome P450 enzymes were examined using commercial screening kits. Results: The in vivo biotransformation of L-P to L-2-Z showed a significant species difference, with a mean elimination half-life t1/2 of approximately 1.4 h in rats and 1.9 h in dogs. The systemic exposure levels of L-P and L-2-Z were increased in a dose-dependent manner. In rats, approximately 66% of L-P and 79% of L-2-Z were bound to plasma proteins. In rats and the nude mice bearing human hepatic cancers, most organ tissues had significantly higher concentrations of L-P than the corresponding plasma levels. In the tumor tissues, the L-P levels were comparable to those of plasma, whereas the L-2-Z levels were lower than the L-P levels. In rats, L-P was eliminated mainly via biliary excretion, but metabolism played an important role in elimination of the intact L-P. Finally, L-P and L-2-Z exerted moderate inhibition on the activity of CYP3A4 in vitro. Conclusion: L-P and L-2-Z have relatively short elimination half-lives and L-P is mainly eliminated via biliary excretion. The species difference in the conversion of L-P to L-2-Z and potential drug-drug interactions due to inhibition of CYP3A4 should be considered in further studies.
Synthesis, characterization, molecular docking and DNA binding studies of Cu(II), Ni(II), Zn(II) and Mn(II) complexes
Hassan,El-Sonbati,El-Desouky
, p. 293 - 307 (2017)
The azo dye ligand of Cyano-6-(p-tolyl)azo-7-hydroxy coumarine (HL) was synthesized by coupling of 3-Cyano-7-hydroxy coumarine with p-toluidine. The ligand (HL) was formed novel complexes (1–4) with the formulae [Cu(L)Cl(OH2)]2H2O, [Ni(L)Cl(OH2)3], [Zn(L)Cl(OH2)]H2O and [Mn(L)Cl(OH2)3]2H2O, respectively. HL and its complexes were characterized by elemental analyses, IR, 1H NMR, MS and UV–Visible spectra as well as magnetic and thermal measurements. The molar conductance measurements proved that all the complexes are non-electrolytes. Also, the important fragments in the ligand and Ni(II) complex were done using mass spectra and the main peaks were corresponding to the molecular weights of them. IR spectra shows that the ligand (HL) act as monobasic bidentate coordinated via nitrogen atom of the azo group ([sbnd]N[dbnd]N[sbnd]) and oxygen atom of the deprotonated phenolic OH group. The Thermal decomposition of the complexes revealed the outer and inner water molecules as well as the end product which in most cases is metal oxide. The thermodynamic parameter of the ligand (HL) and its metal complexes are calculated using Coats-Redfern and Horowitz Metzger methods. The molecular and electronic structures of the investigated compounds were also studied using quantum chemical calculations. The bonding parameter of the complexes have been calculated. Molecular docking was used to predict the binding between azo compounds with the receptor of breast cancer 3hb5-oxidoreductase and prostate cancer mutant 2q7k–Hormone. The calf thymus DNA binding activity of the ligand (HL) and its metal complexes were studied by absorption spectra. The cytotoxic activity of ligand (HL) and its metal complexes was tested against human cancer MCF-7 (breast cancer).
Novel coumarin-based sensitive and selective fluorescent probes for biothiols in aqueous solution and in living cells
Li, Jun,Zhang, Chun-Fang,Ming, Ze-Zhong,Yang, Wen-Chao,Yang, Guang-Fu
, p. 26059 - 26065 (2013)
Two novel coumarin-derived fluorescent probes were designed and synthesized for the quantitative determination of biothiols, such as cysteine (Cys), glutathione (GSH) and homocysteine (Hcy). Both probes selectively and sensitively detected biothiols in vi
Antagonistic activity of hydroxycoumarin-based antioxidants as possible singlet oxygen precursor photosensitizers
Guerrero, Tomás,Vázquez-Ortega, Fernanda,Lagunes, Irene,Ortiz-Blanco, Erik,Sosa-Ortiz, Gabriela,Tovar-Miranda, Ricardo,Medina, Manuel E.,Trigos, ángel
, (2021)
Coumarins are phenolic-type compounds with efficient antioxidant activity due to their ability to scavenge reactive oxygen species. Nevertheless, their ability to behave as photosensitizers capable of generating reactive oxygen species, such as singlet oxygen, has been less studied. In this work, the photosensitizing ability of seven hydroxycoumarins was evaluated through the photooxidation of ergosterol by quantifying the conversion of ergosterol into ergosterol peroxide. In our experimental conditions, we found that almost every tested antioxidant coumarin promotes the peroxidation of ergosterol. The results suggest that the hydroxycoumarins exhibit potential photosensitizing activity by promoting singlet oxygen generation by a Type II photochemical mechanism. Density functional theory (DFT) calculations were also performed to obtain further insight into the chemical reactivity of tested compounds; the observed tendency in the group of antioxidant coumarins to promote the reaction was their hardness due to the principle of maximum hardness. To evaluate our conclusion, we performed the reaction using a highly polarizable coumarin as a photosensitizer, which resulted in an increased photosensitizing capacity supported with DFT calculations, which reinforces our analysis. Finally, we found that hydroxycoumarins can be potentially pro-oxidants since some of them can act as photosensitizers and generate singlet oxygen in the presence of UV–Vis light, a characteristic that must be considered when these compounds are used as antioxidants.
Structure-Activity Relationship Studies of Coumarin-like Diacid Derivatives as Human G Protein-Coupled Receptor-35 (hGPR35) Agonists and a Consequent New Design Principle
Wei, Lai,Hou, Tao,Li, Jiaqi,Zhang, Xiuli,Zhou, Han,Wang, Zhenyu,Cheng, Junxiang,Xiang, Kaijing,Wang, Jixia,Zhao, Yaopeng,Liang, Xinmiao
supporting information, p. 2634 - 2647 (2021/04/02)
A series of coumarin-like diacid derivatives were designed and synthesized as novel agonists of human G-protein-coupled receptor 35 (hGPR35). Active compounds were characterized to possess one acidic group on both sides of a fused tricyclic aromatic scaff
One-Pot Green Synthesis of 2-Oxo-2H-chromene-3-carbonitriles Using Dual-Frequency Ultrasonication
Aruna,Kumar, S.,Sharma, S. P.,Vashisht, N.
, p. 1508 - 1512 (2021/10/26)
Abstract: A green synthesis of 2-oxo-2H-chromene-3-carbonitriles has been carried out in one step by reacting 2-hydroxybenzaldehydes or 2-hydroxyacetophenones with ethyl cyanoacetate under dual-frequency ultrasonica-tion (ultrasonic bath of 40 KHz and probe of 20 KHz). The compounds were obtained in very high yield, and their structures were confirmed by IR and NMR data.
