151889-83-7Relevant academic research and scientific papers
Coumarin-benzothiazole-chlorambucil (Cou-Benz-Cbl) conjugate: An ESIPT based pH sensitive photoresponsive drug delivery system
Barman, Shrabani,Mukhopadhyay, Sourav K.,Gangopadhyay,Biswas, Sandipan,Dey, Satyahari,Singh, N.D.Pradeep
, p. 3490 - 3497 (2015)
We have developed an ESIPT based drug delivery system (DDS), Cou-Benz-Cbl conjugate, by incorporating a benzothiazole group at the 8th position of the 7-hydroxy-coumarin moiety for pH sensitive fluorescence properties and photocontrolled release of the anticancer drug chlorambucil. The Cou-Benz-Cbl conjugate exhibited unique photophysical properties like good absorbance at around 350 nm, a large Stokes shift (～151 nm) and pH sensitive fluorescence properties. The pH sensitive fluorescence properties of the Cou-Benz-Cbl conjugate can be ascribed to an ESIPT turn "on and off" mechanism. At physiological pH, the ESIPT gets turned "off" and a blue fluorescence of the coumarin moiety was observed, but at acidic pH, the ESIPT gets turned "on" and a green fluorescence was noted. Photolysis of the Cou-Benz-Cbl conjugate using UV light of wavelength ≥365 nm resulted in the efficient release of the anticancer drug chlorambucil. Cellular uptake studies revealed that the Cou-Benz-Cbl conjugate was easily internalized inside the cancer cells. Further, an MTT assay showed that the Cou-Benz-Cbl conjugate has a good biocompatibility and low cytotoxicity towards the MDA-MB-231 cell line, whereas upon exposure to UV light, the Cou-Benz-Cbl conjugate exhibited enhanced cytotoxicity compared to the free drug due to the effective release of the anticancer drug chlorambucil inside the cancer cell.
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)
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.
Photoresponsive coumarin polyesters that exhibit cross-linking and chain scission properties
Maddipatla, Murthy V.S.N.,Wehrung, Daniel,Tang, Chuan,Fan, Weizheng,Oyewumi, Moses O.,Miyoshi, Toshikazu,Joy, Abraham
, p. 5133 - 5140 (2013)
The synthesis and properties of a new class of photoresponsive coumarin polyesters are described. Incorporation of the coumarin chromophore in the polymer chain provides interesting properties such as polymer chain cross-linking upon irradiation at 350 nm and chain un-cross-linking when irradiated at 254 nm. In addition, irradiation at 254 nm also results in polymer chain scission. The cross-linking, un-cross-linking, and chain scission properties were studied by ssNMR, ATR-IR, and GPC measurements. These properties enable the fabrication of 2D surfaces having complementary micropatterned features. Also, initial biocompatibility profiles of the polymers and their irradiation products were demonstrated using MTT assays.
Synthesis of meso-coumarin-conjugated porphyrins and investigation of their luminescence properties
Lin, Weiying,Long, Lingliang,Feng, Jianbo,Wang, Bin,Guo, Cancheng
, p. 4301 - 4304 (2007)
A series of meso-coumarin-conjugated porphyrins 1a-e were designed and synthesized. Condensation of 4-chloroacetoacetate ethyl ester with m-cresol or resorcin afforded 4-chloromethylcoumarins, which were then hydrolyzed to give coumarin alcohols, followed by oxidation to provide coumarin aldehydes. The reaction of coumarin aldehydes with pyrrole under Adler or Lindsey conditions afforded the meso-coumarin-conjugated porphyrins 1a-e. Their UV/Vis absorption spectra and photoluminescent spectra were recorded both in dilute THF solution and as solid films. Analysis of the luminescence spectra indicate that the energy transfer from the coumarin substituents to the porphyrin core for 1a-e is more efficient in solid film than in solution, and the energy transfer from the coumarin substituent to the porphyrin core for 1d and 1e is more efficient than that of 1a, 1b and 1c in solid film. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs
Binda, Claudia,Wang, Jin,Pisani, Leonardo,Caccia, Carla,Carotti, Angelo,Salvati, Patricia,Edmondson, Dale E.,Mattevi, Andrea
, p. 5848 - 5852 (2007)
Structures of human monoamine oxidase B (MAO B) in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography. These compounds competitively inhibit MAO B with Ki v
A fluorogenic probe for the copper(I)-catalyzed azide-alkyne ligation reaction: Modulation of the fluorescence emission via 3(n, π*)-1(π,π*) inversion
Zhou, Zhen,Fahrni, Christoph J.
, p. 8862 - 8863 (2004)
Chemoselective ligation reactions represent a powerful approach for labeling of proteins or small molecules in a biological environment. We report here a fluorogenic probe that is activated by click chemistry, a highly versatile bio-orthogonal and chemose
Synthesis and photobiological properties of 4-hydroxymethyl-4'-methylpsoralen derivatives.
Zagotto,Gia,Baccichetti,Uriarte,Palumbo
, p. 486 - 491 (1993)
The synthesis and the photobiological activity of two new hydroxymethyl derivatives of psoralen namely 4-hydroxymethyl-4'-methyl- and 4-hydroxymethyl-4'-methyl-8-methoxypsoralen are described. Both compounds exhibited efficient photobinding to DNA and RNA. The DNA-photobinding process was investigated using different nucleic acid structures such as double-helical DNA, ribosomal RNA, bacterial DNA and DNA organized in the nucleosomal arrangement. The test derivatives were able to induce cross-links to a similar extent as 8-methoxypsoralen (8-MOP), used as a reference photochemotherapeutic drug. In contrast to 8-MOP, they produced relatively high levels of 1O2. Most photobiological effects (DNA synthesis inhibition, T2 phage sensitization, inhibition of tumor transmitting capacity) showed a good correlation with the extent of covalent photoaddition. On the other hand, the new 4-hydroxymethylpsoralens were unable to induce skin erythema, in striking contrast with 8-MOP. Thus, neither cross-linking of the nucleic acid nor 1O2 production were coupled with skin phototoxicity in this class of compounds. The new derivatives appear to represent an important beginning to development of new active photochemotherapeutic agents devoid of undesired phototoxic side effects.
A sequential enzyme-activated and light-triggered pro-prodrug nanosystem for cancer detection and therapy
Chen, Zelin,Li, Bowen,Xie, Xin,Zeng, Fang,Wu, Shuizhu
, p. 2547 - 2556 (2018)
DT-diaphorase is a cytosolic flavoenzyme whose level is strongly elevated in a number of tumor types. Incorporating a DT-diaphorase's substrate in the structure of anticancer drugs may facilitate cancer detection and therapy. Herein, we developed a novel pro-prodrug nanosystem for cancer detection and therapy, which features enzyme-activated fluorescence emission and subsequent light-triggered drug release. The pro-prodrug molecule comprises an anticancer drug methotrexate (MTX), an enzyme (DT-diaphorase) responsive quinone propionic acid moiety and a light-activatable coumarinyl. In the absence of DT-diaphorase, the quinone propionic acid moiety quenches the fluorescence of coumarin via photoinduced electron transfer (PET) and blocks the photocleavage pathway. DT-diaphorase can annihilate the effect of PET and restore the fluorescence of coumarin. This fluorescence serves as the reporting signal for assessing the enzyme biomarker level and discriminates tumor cells from normal cells, and subsequently photocontrollable release of the active drug, MTX, can be activated via one- or two-photon irradiation. This pro-prodrug nanosystem shows strong cytotoxicity toward cancer cells and a negligible effect on normal cells. This strategy provides a new platform for constructing nanosystems for cancer detection and subsequent on-demand selective killing of cancer cells via both internal- and external-stimuli activation.
Practical and Scalable Synthesis of 7-Azetidin-1-yl-4-(hydroxymethyl)coumarin: An Improved Photoremovable Group
Bassolino, Giovanni,Halabi, Elias A.,Rivera-Fuentes, Pablo
, p. 846 - 852 (2018)
7-Substituted 4-methylcoumarin derivatives are widely employed as photoprotecting groups in chemistry and biology. We have recently shown that the 7-azetidinylated version of this photocage releases carboxylic acids in aqueous solution more efficiently than the traditionally used 7-diethylamino variant. Here we present a robust and scalable route to prepare the 7-azetidinylated alcohol, a useful precursor for the photoprotection of a variety of leaving groups, and its use in the preparation of model phosphate, sulfonate, and carbamate derivatives.
6-Bromo-7-hydroxy-3-methylcoumarin (mBhc) is an efficient multi-photon labile protecting group for thiol caging and three-dimensional chemical patterning
Mahmoodi, M. Mohsen,Fisher, Stephanie A.,Tam, Roger Y.,Goff, Philip C.,Anderson, Reid B.,Wissinger, Jane E.,Blank, David A.,Shoichet, Molly S.,Distefano, Mark D.
, p. 8289 - 8300 (2016)
The photochemical release of chemical reagents and bioactive molecules provides a useful tool for spatio-temporal control of biological processes. However, achieving this goal requires the development of highly efficient one- and two-photon sensitive photo-cleavable protecting groups. Thiol-containing compounds play critical roles in biological systems and bioengineering applications. While potentially useful for sulfhydryl protection, the 6-bromo-7-hydroxy coumarin-4-ylmethyl (Bhc) group can undergo an undesired photoisomerization reaction upon irradiation that limits its uncaging efficiency. To address this issue, here we describe the development of 6-bromo-7-hydroxy-3-methylcoumarin-4-ylmethyl (mBhc) as an improved group for thiol-protection. One- and two-photon photolysis reactions demonstrate that a peptide containing a mBhc-caged thiol undergoes clean and efficient photo-cleavage upon irradiation without detectable photoisomer production. To test its utility for biological studies, a K-Ras-derived peptide containing an mBhc-protected thiol was prepared by solid phase peptide synthesis using Fmoc-Cys(mBhc)-OH for the introduction of the caged thiol. Irradiation of that peptide using either UV or near IR light in presence of protein farnesyltransferase (PFTase), resulted in generation of the free peptide which was then recognized by the enzyme and became farnesylated. To show the utility of this caging group in biomaterial applications, we covalently modified hydrogels with mBhc-protected cysteamine. Using multi-photon confocal microscopy, highly defined volumes of free thiols were generated inside the hydrogels and visualized via reaction with a sulfhydryl-reactive fluorophore. The simple synthesis of mBhc and its efficient removal by one- and two-photon processes make it an attractive protecting group for thiol caging in a variety of applications.
