Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabine

Pignatello, Rosario; Vicari, Luisa; Pistarà, Venerando; Musumeci, Teresa; Gulisano, Massimo; Puglisi, Giovanni

doi:10.1002/ddr.20374

Cited by 7 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are several reports on the cytotoxicity studies of the prodrugs derived from lipoamino acids whereas reports on cytotoxicity of only lipoamino acids are very scarce 19 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Lipoamino Acid Conjugates of Sapienic Acid and Evaluation of Their Cytotoxicity Activities

et al. 2014

View full text Add to dashboard Cite

“…There are several reports on the cytotoxicity studies of the prodrugs derived from lipoamino acids whereas reports on cytotoxicity of only lipoamino acids are very scarce 19 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Lipoamino Acid Conjugates of Sapienic Acid and Evaluation of Their Cytotoxicity Activities

et al. 2014

View full text Add to dashboard Cite

“…Besides conjugation with polymeric materials, 211,212 the preparation of N 4 -derivatives with lipoaminoacid residues, suitable for penetration through biological membranes and barriers, was also reported. 213 Lipoaminoacids are aminoacids bearing an alkyl chain in the 2-position. They impart to the molecule to which they are conjugated amphiphilic 945 properties.…”

Section: Scheme 102mentioning

confidence: 99%

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

Ferraboschi

Ciceri

Grisenti

2017

Organic Preparations and Procedures International

View full text Add to dashboard Cite

5-Fluorouracil35 Interest in the fluoropyrimidines stemmed from studies of the metabolism of uracil in rat hepatoma cells. The observation that these cells utilize uracil more avidly than normal rat intestinal mucosa prompted the preparation of fluorinated pyrimidines in order to improve disruption of tumor DNA biosynthesis. 3 In 1957 5-fluorouracil (5-FU) 1 was synthesized by Heidelberger et al., 4 with the aim of 40 blocking metabolism in malignant cells. The replacement of a hydrogen atom at C-5 by the fluorine atom modifies the interaction with the active sites of enzymes involved in metabolism. This antimetabolite, although toxic, is still one of the most widely used agents against solid tumors. Its action is due to two different mechanisms: 5 after penetration into the cell, 5-FU 1 is transformed into the 5-fluorouridine triphosphate that mimics UTP, is recognized by RNA 45 polymerase and consequently incorporated into RNA. The most significant action, however, is due to the 5-FU conversion into 5-fluoro-2 0 -deoxyuridine (FdUMP) 2, a known inhibitor of thymidylate synthetase (TS), a key enzyme in the DNA synthesis. 6,7 TS, in the presence of methylene tetrahydrofolate and deoxyuridine monophosphate (dUMP) 3 forms a ternary complex that catalyzes the substitution of 5-H uracil with a methyl group, affording thymine. If FdUMP 50 2 is present, the above ternary complex is not able to carry out this reaction, due to the presence of fluorine in the 5-position: the formation of TMP 4 (2 0 -deoxythymidine 5 0 -monophosphate), the only nucleotide precursor specific to DNA, is, therefore, blocked (Scheme 1), decreasing the availability of TTP (2 0 -deoxythymidine 5 0 -triphosphate) for DNA synthesis.Scheme 1 2 Ferraboschi, Ciceri, and GrisentiLater two additional mechanisms were proposed for 5-FU 1 antitumor activity: the 55 incorporation of 5-FU into DNA and the alteration of the membrane function of 5-FU 1 treated cells. Recent studies indicate that the TS-direct mechanism predominates when 1 is administered at low doses for a prolonged time, whereas the RNA-mediated process is more active following a bolus administration. 8-10 Synthesis of 5-FU 1, by construction of the pyrimidine ring, was first realized by Hei-60 delberger et al. in 1957 4,11,12 by reaction of a thiourea derivative 5 with the enolate of ethyl a-fluoro, a-formyl acetate 6 which, in turn, was obtained from methyl formate and ethyl fluoroacetate (Scheme 2). Depending on the chosen a-fluoro-b-ketoester the method is also applicable to the synthesis of other 5-fluoropyrimidines.An alternative method for the total synthesis is the direct fluorination of the pyrimi-65 dine ring of compound 7 by means of trifluoromethyl hypofluorite (CF 3 OF) 13 proposed by Robins in 1971. In the case of CF 3 OF in methanol/fluorotrichloromethane an intermediate was formed that, after treatment with triethylamine, afforded 5-FU 1 in 84% yield. 13 If the reaction was carried out with CF 3 OF in trifluoroacetic acid 1 was directly isolated in 85% yield. 14 The meth...

show abstract

Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation

et al. 2011

View full text Add to dashboard Cite

Trialkylammonium 4-(N)-1,1Ј,2-trisnor-squalenoylgemcitabine monophosphate (SQdFdC-MP) salts were prepared from 1,1Ј,2-trisnor-squalenoylgemcitabine by phosphoramiditetype chemistry. This amphiphilic molecule self-assembled into nanoassemblies of about 100 nm in size in aqueous solutions. Cryo-TEM and small-angle X-ray scattering (SAXS) investigations revealed that SQdFdC-MP molecules selforganized into unilamellar liposomes with a membrane

show abstract

Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabine

Cited by 7 publications

References 39 publications

Synthesis of Novel Lipoamino Acid Conjugates of Sapienic Acid and Evaluation of Their Cytotoxicity Activities

Synthesis of Novel Lipoamino Acid Conjugates of Sapienic Acid and Evaluation of Their Cytotoxicity Activities

Synthesis of Antitumor Fluorinated Pyrimidine Nucleosides

Squalenoyl Gemcitabine Monophosphate: Synthesis, Characterisation of Nanoassemblies and Biological Evaluation

Contact Info

Product

Resources

About