34905-02-7Relevant articles and documents
Maximizing the thiol-activated photodynamic and fluorescence imaging functionalities of theranostic reagents by modularization of Bodipy-based dyad triplet photosensitizers
Zhao, Jianzhang,Huang, Ling,Cui, Xiaoneng,Li, Shujing,Wu, Huijian
, p. 9194 - 9211 (2015)
To maximize both the activatable singlet oxygen (1O2) production and fluorescence of theranostic photodynamic (PDT) reagents, herein we propose a modularized molecular structural profile, i.e. the intersystem crossing (ISC) and fluorescence functionalities were accomplished with different modules in a dyad, thus enabling the activated 1O2 production yield (ΦΔ, PDT) and the fluorescence yield (ΦF) to both approach 100%. The PDT and the fluorescence were caged with a thiol-cleavable disulfide bond (-S-S-) linker and an electron trap (2,4-dinitrobenzenesulfide, DNBS). This new molecular structural profile is different from that of conventional theranostic PDT reagents, which are based on a single chromophore for both PDT and fluorescence; thus, the limitation of ΦΔ + ΦF = 100% exists for only half of our new molecular profile. To this end, six Bodipy dyads were prepared. The photophysical properties of the dyads were studied with steady state absorption, fluorescence and nanosecond transient absorption spectroscopy. The dyads show weak PDT and luminescence, due to the caging effect. In the presence of thiols (GSH or Cys), cleavage of the disulfide linker and DNBS occurs, and the PDT and fluorescence modules are activated simultaneously (ΦF: 1.3% → 47.6%; ΦΔ: 16.7% → 71.5%). These results are useful in designing activatable PDT/fluorescence imaging theranostic reagents.
Design, synthesis, anticancer and antioxidant activities of amide linked 1,4-disubstituted 1,2,3-triazoles
Das, Ashutosh,Kaushik, C. P.,Kumar, Ashwani,Kumar, Deepak,Kumar, Devinder,Luxmi, Raj,Sangwan, Jyoti,Singh, Dharmendra
, (2020/10/08)
To explore anticancer and antioxidant agents with improved potency, we synthesized a series of amide linked 1,4-disubstituted 1,2,3-triazoles through click chemistry approach. The structure of synthesized triazoles were characterized by- FTIR, 1H NMR, 13C NMR spectroscopy and HRMS. All the synthesized compounds were screened for their anticancer activity against four different cell lines- PC3 (prostate cancer), A549 (lung cancer), MIAPACA (liver cancer), Fr2 (Breast epithelial), reflecting compounds 7e and 7f to possess good activity. The antioxidant activity was evaluated by using stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and compound 7d showed promising activity having IC50 value 1.61 μg/ml. Molecular docking studies of compounds 7e and 7f was carried out in active site of human epidermal growth factor receptor 2 revealed high binding affinities and within toxicity limits. The experimental results were in good agreement with docking studies. In-silico ADME studies of synthesized compounds also have good dispositional profile and are patient compliant, may be potential future candidates for anticancer treatment.
Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C-C Bond Insertion
Alegre-Requena, Juan V.,De Lescure, Louis,Modak, Atanu,Paton, Robert S.,Race, Nicholas J.,Rynders, Kathryn J.
supporting information, (2021/12/27)
The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated"C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization. Computational analysis provides critical insight into the reaction mechanism, in particular the key selectivity-determining step.
A new NT4 peptide-based drug delivery system for cancer treatment
Bracci, Luisa,Brunetti, Jlenia,Cipriani, Giulia,Depau, Lorenzo,Falciani, Chiara,Fragai, Marco,Menichetti, Stefano,Piantini, Sara,Pini, Alessandro,Scali, Silvia
, (2020/03/13)
The development of selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetr
1,2,3-Triazole-based kojic acid analogs as potent tyrosinase inhibitors: Design, synthesis and biological evaluation
Ashooriha, Morteza,Khoshneviszadeh, Mehdi,Khoshneviszadeh, Mahsima,Moradi, Seyed Ershad,Rafiei, Alireza,Kardan, Mostafa,Emami, Saeed
, p. 414 - 422 (2018/11/21)
A series of kojic acid-derived compounds 6a-p bearing aryloxymethyl-1H-1,2,3-triazol-1-yl moiety were designed by modifying primary alcoholic group of kojic acid as tyrosinase inhibitors. The target compounds 6a-p were synthesized via click reaction. All
Synthesis and Evaluation of O 2-Derived Diazeniumdiolates Activatable via Bioorthogonal Chemistry Reactions in Living Cells
Lv, Tian,Wu, Jianbing,Kang, Fenghua,Wang, Tingting,Wan, Boheng,Lu, Jin-Jian,Zhang, Yihua,Huang, Zhangjian
supporting information, p. 2164 - 2167 (2018/04/30)
A class of O2-alkyl derived diazeniumdiolates 3a-f and 4a-c were designed and synthesized as new bioorthogonal NO precursors, which can be effectively uncaged in the presence of a palladium catalyst via bioorthogonal bond cleavage reactions to generate NO in living cancer cells, eliciting potent antiproliferative activity.
Efficient Multicomponent Active Template Synthesis of Catenanes
Lewis, James E. M.,Modicom, Florian,Goldup, Stephen M.
supporting information, p. 4787 - 4791 (2018/04/17)
We describe a simple and high yielding active template synthesis of [2]catenanes. In addition to mechanical bond formation using a single premacrocycle bearing an azide and alkyne moiety, our method is also suitable for the co-macrocyclization of readily
Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium-Functionalized Microdevices
Adam, Catherine,Pérez-López, Ana M.,Hamilton, Lloyd,Rubio-Ruiz, Belén,Bray, Thomas L.,Sieger, Dirk,Brennan, Paul M.,Unciti-Broceta, Asier
supporting information, p. 16783 - 16790 (2018/11/23)
SN-38, the active metabolite of irinotecan, is released upon liver hydrolysis to mediate potent antitumor activity. Systemic exposure to SN-38, however, also leads to serious side effects. To reduce systemic toxicity by controlling where and when SN-38 is generated, a new prodrug was specifically designed to be metabolically stable and undergo rapid palladium-mediated activation. Blocking the phenolic OH of SN-38 with a 2,6-bis(propargyloxy)benzyl group led to significant reduction of cytotoxic activity (up to 44-fold). Anticancer properties were swiftly restored in the presence of heterogeneous palladium (Pd) catalysts to kill colorectal cancer and glioma cells, proving the efficacy of this novel masking strategy for aromatic hydroxyls. Combination with a Pd-activated 5FU prodrug augmented the antiproliferative potency of the treatment, while displaying no activity in the absence of the Pd source, which illustrates the benefit of achieving controlled release of multiple approved therapeutics—sequentially or simultaneously—by the same bioorthogonal catalyst to increase anticancer activity.
The synthesis and ring-opening metathesis polymerization of glycomonomers
Weaver, Lucy G.,Singh, Yogendra,Burn, Paul L.,Blanchfield, Joanne T.
, p. 31256 - 31264 (2016/04/08)
The synthesis of a series of short poly(norbornene)s displaying pendant disaccharides is reported. para-(Propargyloxy)benzyl moieties were attached to a norbornenyl group via an ester or amide linkage, giving two different pre-monomers. A set of protected β-(1→6)-linked glucosamine-based disaccharides, structurally similar to the bacterial biofilm constituent poly-N-acetylglucosamine (PNAG), were attached to the pre-monomers via a Huisgen 1,3-dipolar cycloaddition reaction to generate a series of 'glycomonomers'. In the presence of a Grubbs' 3rd generation catalyst, the glycomonomers displayed variable reactivities that were dependent on the type of linkage (ester or amide) between the norbornenyl and benzyl moieties. In general, the amide-linked glycomonomers polymerized at a much slower rate and had a comparatively lower degree of polymerization than the corresponding ester-linked constructs. All the materials displayed a relatively narrow molecular weight distribution ( = 1.2-1.5).
Substituted 4-(1H-1,2,3-triazol-1-yl)-tetrafluorobenzoates: Selective synthesis and structure
Solodukhin, Nikolai N.,Borisova, Nataliya E.,Churakov, Andrei V.,Zaitsev, Kirill V.
, p. 15 - 23 (2016/06/01)
Regioselective, simple and fast synthesis of a series of [2 + 3]-cycloaddition products, 2-11, 4-(4-RC2HN3)C6F4CO2Et (2: R = Ph; 3: R = CMe2OH; 4: R = CH2OH; 5: R = CO2Et; 6: R = n-C5H11; 7: R = CH2O-o-C6H4CHO; 8: R = CH2O-p-C6H4NHBoc; 9: R = CH2O-p-C6H4CH2OH; 10: R = CH2O2CC6F5; 11: R = p-C6H4Bu-t), in reaction between ethyl 4-azido-2,3,5,6-tetrafluorobenzoate, 1, and a number of substituted alkynes was elaborated under conditions of copper-catalyzed click chemistry reaction. The optimized conditions include application of CuBr and Et3N in dichloromethane. The structure of compounds 2-11 was investigated in solution by 1D and 2D NMR and IR spectroscopy. The molecular structure of 2 in solid state was established by X-ray analysis.
