Synthesis, Characterization, and In Vitro Assay of Folic Acid Conjugates of 3′-Azido-3′-Deoxythymidine (AZT): Toward Targeted AZT Based Anticancer Therapeutics

Vortherms, Anthony R.; Doyle, Robert P.; Gao, Dayuan; Debrah, Olivia; Sinko, Patrick J.

doi:10.1080/15257770701795946

Cited by 16 publications

(17 citation statements)

References 38 publications

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“…These isomers were separated by ionexchange chromatography and characterized as described previously. [14] Such separation is necessary to remove the inactive a-1 system, which is not recognized by the FR. [15] Compound 2 was prepared by reductive amination of two moles of quinoline-2-carboxaldehyde and the amino acid linker, 5-aminovaleric acid as previously described and shown in Scheme 2.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

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Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells

et al. 2008

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The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA-PEG-BQAV-Re(CO)3]+ (gamma-4) was screened against an adriamycin- and cisplatin-resistant human ovarian cancer cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound gamma-4 was internalized by a folate-receptor-mediated endocytotic pathway, which results in internal accumulation of gamma-4. This was contrasted with a FR-negative Chinese hamster ovary cell line in which no internalization of gamma-4 was observed. gamma-4 was found to be cytotoxic with IC(50) values of 189 and 78 microM at 6 and 24 h, respectively, toward the FR-positive cell line. This is in contrast to the IC(50) value of 502 microM at 6 h and 84 microM at 24 h for cisplatin in the same cell line, with a significantly greater toxicity at the earlier time point. The cytotoxicity of gamma-4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described.

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Section: Synthesis and Characterizationmentioning

confidence: 99%

“…[39] The isomers, a-and g-of 1 were purified by using a procedure that was established in our research group. [14] Synthesis of {[bis(quinolin-2-ylmethyl)amino]-5-valeric acid} (BQAV) (2): Compound 2 was prepared by using a previously established procedure. [16] 5-aminovaleric acid (0.633 g, 5.4 mmol) was dissolved in DCE (20 mL).…”

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confidence: 99%

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells

et al. 2008

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“…In addition, folate moiety plays an important role in providing pH‐responsive properties. Folate content of MM3 was lower than the other mixed micelles (Table ); nevertheless, the binding constant between folate and folate receptor expressed on the membrane of cancer cells was reported to be around 0.1—1 × 10 −9 m , indicating MM3 mixed micelles still have high affinity to the folate receptor‐expressing cancer cells.…”

Section: Resultsmentioning

confidence: 89%

Folate‐Conjugated and Dual Stimuli‐Responsive Mixed Micelles Loading Indocyanine Green for Photothermal and Photodynamic Therapy

Chien

Wang

Liao

et al. 2018

Macromolecular Bioscience

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A folic acid targeted mixed micelle system based on co-assembly of poly(ε-caprolactone)-b-poly(methoxytri(ethylene glycol) methacrylate-co-N-(2-methacrylamido)ethyl folatic amide) and poly(ε-caprolactone)-b-poly(diethylene glycol monomethyl ether methacrylate) is developed to encapsulate indocyanine green (ICG) for photothermal therapy and photodynamic therapy. In this study, the use of folic acid is not only for specific cancer cell recognition, but also in virtue of the carboxylic acid on folic acid to regulate the pH-dependent thermal phase transition of polymeric micelles for controlled drug release. The prepared ICG-loaded mixed micelles possess several superior properties such as a preferable thermoresponsive behavior, excellent storage stability, and good local hyperthermia and reactive oxygen species generation under near-infrared (NIR) irradiation. The photototoxicity induced by the ICG-loaded micelles has efficiently suppressed the growth of HeLa cells (folate receptor positive cells) under NIR irradiation compared to that of HT-29, which has low folate receptor expression. Hence, this new type of mixed micelles with excellent features could be a promising delivery system for controlled drug release, effective cancer cell targeting, and photoactivated therapy.

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“…There is an active γ-isomer and an inactive α-isomer produced by tandem coupling through the α-, and γ-carboxylic acids of FA or MTX. The MTX-PEG building block ( 1 ) was synthesized using a similar approach to that used by us for the preparation of Folate-PEG-NH 2 12. The desired γ-isomer was then purified by ion exchange chromatography using an ANX column.…”

Section: Resultsmentioning

confidence: 99%

Anticancer Conjugates and Cocktails Based on Methotrexate and Nucleoside Synergism

Vortherms

Dang

Doyle

2009

Clinical medicine. Oncology

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Abstract:Conjugates of methotrexate (MTX) and the nucleoside analogs 3-azidodeoxythymidine (AZT), iododeoxyuridine (IUdR) and dideoxycytidine (ddC) linked using poly(ethyleneglycol) are presented. In vitro cytotoxicity assays of the conjugates against drug resistant ovarian cell line A2780/AD are preformed and comparisons made to such assays performed for unconjugated (cocktail) systems. All systems tested were inactive, or had low activity, at 24 h. After 72 hr incubation however, the cocktails of MTX and AZT, IUdR or ddC showed high cytotoxicity in the low nanomolar range. The conjugates were only very moderately active with IC 50 values in the [0.1 to 1.0 mM] range. Conjugation of the antifolate to the nucleoside analogs has it seems reduced the activity signifi cantly when compared to a cocktail of the components, indicating a conjugate approach is unlikely to translate into success in vivo. The positive note comes from the observation that by combining two of the new conjugates, namely those based on MTX with IUdR or AZT, an IC50 at 24 hours of ∼ [180 μM] was produced.

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Synthesis, Characterization, and In Vitro Assay of Folic Acid Conjugates of 3′-Azido-3′-Deoxythymidine (AZT): Toward Targeted AZT Based Anticancer Therapeutics

Cited by 16 publications

References 38 publications

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells

Folate‐Conjugated and Dual Stimuli‐Responsive Mixed Micelles Loading Indocyanine Green for Photothermal and Photodynamic Therapy

Anticancer Conjugates and Cocktails Based on Methotrexate and Nucleoside Synergism

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Synthesis, Characterization, and In Vitro Assay of Folic Acid Conjugates of 3′-Azido-3′-Deoxythymidine (AZT): Toward Targeted AZT Based Anticancer Therapeutics

Cited by 16 publications

References 38 publications

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of ReI Conjugates in FR‐Overexpressing Cancer Cells

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of ReI Conjugates in FR‐Overexpressing Cancer Cells

Folate‐Conjugated and Dual Stimuli‐Responsive Mixed Micelles Loading Indocyanine Green for Photothermal and Photodynamic Therapy

Anticancer Conjugates and Cocktails Based on Methotrexate and Nucleoside Synergism

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Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells

Targeting the Folate Receptor (FR): Imaging and Cytotoxicity of Re^I Conjugates in FR‐Overexpressing Cancer Cells