Synthesis of 3′-azido-3′-deoxythymidine (AZT)—Cinchona alkaloid conjugates via click chemistry: Toward novel fluorescent markers and cytostatic agents

Baraniak, Dagmara; Kacprzak, Karol; Celewicz, Lech

doi:10.1016/j.bmcl.2010.11.127

Cited by 46 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 H NMR (Indian Institute of Technology, Chennai) spectra of all the monomer and polymer samples in CDCl 3 were recorded on a Bruker 300 MHz FT NMR spectrometer at room temperature using tetramethylsilane as an internal standard. The proton-decoupled 13 C NMR (Indian Institute of Technology, Chennai) spectrum was run on the same instrument operating at 22.63 MHz at room temperature, and the chemical shifts were recorded under similar conditions. Thermogravimetric analysis (Indian Institute of Technology, Chennai) was performed using a NETZSCH STA 409C = CD thermal analyzer in air at a heating rate of 10°C/min.…”

Section: Characterization Techniquesmentioning

confidence: 99%

Cinchonidinyl-Based Acrylic and Methacrylic Homopolymers: Synthesis, Characterization, and Antibacterial Activity

Kumar

Mageswari

Nithya

et al. 2015

Adv. Polym. Technol.

View full text Add to dashboard Cite

ABSTRACT:The monomers (5-ethenyl-1-azabicyclo [2.2.2] octan-2-yl)-quinolin-4-ylmethyl acrylate (EAOQMA) and (5-ethenyl-1-azabicyclo [2.2.2] octan-2-yl)-quinolin-4-ylmethyl methacrylate (EAOQMMA) were synthesized by reacting (5-ethenyl-1-azabicyclo octan-2-yl)-quinolin-4-ylmethanol [cinchonidine] with acryloylchloride and methacryloyl chloride, respectively, in the presence of triethylamine. The homopolymers were synthesized by the free radical polymerization in tetrahydrofuran at 70 ± 2°C in nitrogen atmosphere using 2,2 -azobisisobutyronitrile as an initiator. The monomers and homopolymers were characterized by UltraViolet (UV), Fourier transform infrared, Proton-Nuclear Magnetic Resonance ( 1 H NMR), and Carbon-13 Nuclear Magnetic Resonance ( 13 C NMR) spectroscopic techniques. The glass transition temperature (T g ,°C) was determined by differential scanning calorimetry. The thermal stability of the poly(EAOQMMA) was performed by thermogravimetric analysis, which showed higher thermal stability of about 706°C than that of poly(EAOQMA). The antibacterial activity of monomers and polymers has been evaluated by determining the inhibitory zone diameters against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa), in which cinchonidine acrylate and Cinchonidine methacrylate homopolymer showed better activity than their corresponding monomers. Surface morphology of the monomers and polymers were examined by Scanning Electron Microscope (SEM) analysis. C

show abstract

Section: Characterization Techniquesmentioning

confidence: 99%

Cinchonidinyl-Based Acrylic and Methacrylic Homopolymers: Synthesis, Characterization, and Antibacterial Activity

Kumar

Mageswari

Nithya

et al. 2015

Adv. Polym. Technol.

View full text Add to dashboard Cite

show abstract

“…Preliminary in vivo studies within a subcutaneous liver tumor xenograft model showed that dT‐QX inhibits the growth of tumors with EC 50 values in the range of 6.6–42 μ m . The scope of the nucleoside bioconjugates has been elaborated by the incorporation of the Cinchona alkaloids ( 30 ), which were used as fluorescent markers and exhibited in vitro cytotoxicity in human KB (nasopharynx carcinoma) tumor tissue culture …”

Section: Nucleoside and Nucleotide Bioconjugates In Cancer Therapymentioning

confidence: 99%

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

et al. 2015

View full text Add to dashboard Cite

Nucleoside- and nucleotide-based chemotherapeutics have been used to treat cancer for more than 50 years. However, their inherent cytotoxicities and the emergent resistance of tumors against treatment has inspired a new wave of compounds in which the overall pharmacological profile of the bioactive nucleic acid component is improved by conjugation with delivery vectors, small-molecule drugs, and/or imaging modalities. In this manner, nucleic acid bioconjugates have the potential for targeting and effecting multiple biological processes in tumors, leading to synergistic antitumor effects. Consequently, tumor resistance and recurrence is mitigated, leading to more effective forms of cancer therapy. Bioorthogonal chemistry has led to the development of new nucleoside bioconjugates, which have served to improve treatment efficacy en route towards FDA approval. Similarly, oligonucleotide bioconjugates have shown encouraging preclinical and clinical results. The modified oligonucleotides and their pharmaceutically active formulations have addressed many weaknesses of oligonucleotide-based drugs. They have also paved the way for important advancements in cancer diagnosis and treatment. Cancer-targeting ligands such as small-molecules, peptides, and monoclonal antibody fragments have all been successfully applied in oligonucleotide bioconjugation and have shown promising anticancer effects in vitro and in vivo. Thus, the application of bioorthogonal chemistry will, in all likelihood, continue to supply a promising pipeline of nucleic acid bioconjugates for applications in cancer detection and therapy.

show abstract

“…Click chemistry [ 26 ] has recently attracted great attention from the medicinal chemists primarily in the field of triazolyl analog synthesis of natural products including alkaloids [ 27 , 28 ], coumarins [ 29 , 30 ], saponins [ 31 ], steroids [ 32 ] and triterpenes [ 33 ]. Triazole derivatives have a great reputation in medicinal chemistry and have been successfully used as antiviral, antibacterial, antifungal, anti-tuberculosis, anticonvulsant, antidepressant, anti-inflammatory and anticancer agents [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Activity guided isolation and modification of juglone from Juglans regia as potent cytotoxic agent against lung cancer cell lines

Zhang

Zou

Duan

et al. 2015

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundJuglans regia has been found to exhibit significant anticancer activity against various human cancer cell lines. This study was undertaken to isolate the active chemical constituent (Juglone) and to investigate its cytotoxic activity along with its various analogs against different human cancer cell lines.MethodsIsolation of juglone, a napthoquinone, from the chloroform extract of the root part of Juglans regia was executed by flash chromatography using silica gel as stationary phase. The isolated Juglone was used as starting material for the further synthesis of a novel series of triazolyl analogs using click chemistry approach to investigate their cytotoxic potential against different human cancer cell lines using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay.ResultsThe different extracts of Juglans regia and the isolated compound (juglone) exhibited satisfactory cytotoxic activity against a panel of eight different human cancer cell lines namely, prostate colon (Colo-205 and HCT-116), breast (T47D), prostate (PC-3 and DU-145), skin (A-431) and lung (NCI-H322 and A549). Interestingly, all the synthesised analogs displayed enhanced and selective cytotoxic activity against lung cancer cell lines only. Of the synthesized derivatives, 15a and 16a displayed the best activity with IC50 of 4.72 and 4.67 μM against A549 cells. Both these derivatives exhibited superior potency to BEZ-235 against both the lung cancer cell lines. So far as the structural aspects are concerned, electron withdrawing substituents at the ortho position of R moiety of the triazolyl analogs seem to be essential for attaining better activity.ConclusionThe present study demonstrates the selective and enhanced cytotoxic activity of the triazolyl analogs of juglone against NCI-H322 and A549 human lung cancer cell lines. Some derivatives exhibited superior potency to BEZ-235, a commercially available anticancer agent.

show abstract

Synthesis of 3′-azido-3′-deoxythymidine (AZT)—Cinchona alkaloid conjugates via click chemistry: Toward novel fluorescent markers and cytostatic agents

Cited by 46 publications

References 31 publications

Cinchonidinyl-Based Acrylic and Methacrylic Homopolymers: Synthesis, Characterization, and Antibacterial Activity

Cinchonidinyl-Based Acrylic and Methacrylic Homopolymers: Synthesis, Characterization, and Antibacterial Activity

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

Activity guided isolation and modification of juglone from Juglans regia as potent cytotoxic agent against lung cancer cell lines

Contact Info

Product

Resources

About