Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer

Ünak, Turan; Ünak, Perıhan; Ongun, Binnur; Duman, Yusuf

doi:10.1016/s0969-8043(96)00318-1

Cited by 16 publications

(6 citation statements)

References 19 publications

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“…Thus direct condensation of aniline or p-phenylenediamine with sodium D-glucuronate followed by pH adjustment with Dowex-50W-8X gave the N-glucuronides directly, in unspecied yield; 132 I labelled versions of these glucuronides were used as prodrugs in chemotherapy. 179 A related O-glucuronide of 8-hydroxy-5-iodoquinoline 162 was obtained by microsomal incubation. The mono-N-glucuronide of proavine 163 was also obtained by direct condensation with GlcA; 180 N 0 -acetylation of this product afforded a bismetabolite identical with ex vivo material.…”

Section: Neutral N-glucuronidesmentioning

confidence: 99%

Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides

Stachulski

Meng

2013

Nat. Prod. Rep.

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Covering: 1998 to 2011. Previous review: Nat. Prod. Rep., 1998, 15, 173-186. The fourteen years that have passed since the previous review on this topic have seen a significant increase of interest in many aspects of glucuronide chemistry and biology. Glucuronides are the most important class of phase 2 xenobiotic metabolites and typically act in a detoxifying role. While this is generally true for O-alkyl and O-aryl glucuronides, a number of glucuronides are known to be pharmacologically active per se. Additionally the use of glucuronide prodrugs, notably to ameliorate the cytotoxicity of anticancer agents, has markedly increased. Whereas the previous review covered only the synthesis of O-glucuronides, we now include N-, S- and C-glucuronides also and discuss both synthetic and biological aspects. Synthetic methods for all classes of glucuronides are reviewed and updated, together with advances in the enzymatic synthesis of glucuronides and methods for their detection. Finally we discuss the biological reactivity of glucuronides where known, including the important morphine-6-glucuronide. A lively debate has continued for several years on whether O-acyl glucuronide metabolites of carboxylic acids are toxic, affecting both the safety assessment of well-used drugs and new drug development programmes. We summarise the current understanding, together with other known examples of interaction between glucuronides and macromolecules.

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Section: Neutral N-glucuronidesmentioning

confidence: 99%

Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides

Stachulski

Meng

2013

Nat. Prod. Rep.

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“…It has been used to label various biomolecules [14][15][16][17][18] such as proteins, peptides, and antibodies [19,20]. Regarding with Lec, V. Album agglutinin [21], phytohemagglutinin-L [22], and Viscum album agglutinin-I Lec [21] were labeled with 125 I via iodogen method to show receptor ligand interactions.…”

Section: Radioiodinationmentioning

confidence: 99%

Radioiodine labeled CdSe/CdS quantum dots: Lectin targeted dual probes

et al. 2014

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CdSe/CdS quantum dots (QD) were synthesized and bioconjugated with Sambucus nigra agglutinin (SNA) lectin (Lec). Mannose triflate and cysteamine molecules (MTC) were also utilized to prepare MTC-QDs and MTCQDs-Lec probes as well as Lec bound QDs. Afterwards; potential use of these nanoparticles as radiolabeled fluorescence nano-probes for the cell imaging studies has been investigated. Biological activities of 125 I − , 125 I-MTCQDs, MTC-QDs-Lec-125 I, QDs-Lec-125 I and Lec-125 I were examined on various cancer cell lines such as Caco-2, MCF-7 and A-549 in terms of cell incorporation. QDs-Lec-125 I exhibited the highest cell incorporation on whole celllines. In addition, the QDs-Lec-131 I, was used for in vivo imaging. The whole body distribution of the radiolabeled QDs on New Zealand rabbits and Balb C mice were examined by taking dynamic and static images. Radioactivity cleared from the kidneys and the bladder, while significant amount radioactivity was retained in the heart and liver within 24 h.

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“…For this reason, many investigators have tried to develop more cytotoxic and more selective aglycones specific to different tumor types. Aniline [74,85] Phenylenediamine [74] Benzylamine [87] Phenathylamine [87] Ethylamine [87] having high level of radiotoxic character. It is also evident that the radionuclide should be labeled to aglycone portion of the prodrug; in this way, aglycone and radionuclide will be together transported into the cancer cell.…”

Section: Glucuronide Prodrugs and β-Glucuronidasementioning

confidence: 99%

“…In this context, some studies have recently been carried out by Unak et al [73][74][75][76] on the synthesis and radioiodination of some glucuronide conjugates such as phenyl-N-glucuronide, p-phenylene-Nglucuronide, β-naphthyl-O-glucuronide, 8-hydroxyquinolyl-O-glucuronide, p-aniline-mustard-N-and O-glucuronides, etc. (Fig.…”

Section: Comparison Of the Radiotoxicity Levels Of Iodine-125 And Astmentioning

confidence: 99%

Potential Use of Radiolabeled Glucuronide Prodrugs with Auger and/or Alpha Emitters in Combined Chemo- and Radio-Therapy of Cancer

Ünak

2000

CPD

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Nowadays, the scientists from different disciplines have focused their attentions to new anticancer drug design for cancer chemotherapy. An effective anticancer drug should ensure the selective drug incorporation into the targeted tumor cells without principally incorporation into the normal cells. So, the targeted tumor cells can selectively be damaged by the cytotoxic effectiveness of the drug. The basic principles of drug design have involved "prodrug" concept, which means a chemical agent which is not itself active as an anticancer drug, but it can be transformed to an active form after its administration. Prodrugs can finally be activated onto the tumor cells by some kind of enzymes. In this context, the activation of glucuronide prodrugs by b-glucuronidase have a large potential applications in cancer chemotherapy. On the other hand, combined chemo- and radio-therapy of cancer (CCRTC) concept aims to combine the cytotoxicity of an aglycone with the radiotoxicity of an appropriate radionuclide on the same prodrug. So, the cytotoxic and radiotoxic effectiveness' will be able to be concentrated into the same tumor cell to increase obviously its damage. For experimental realization of this concept an effective anticancer prodrug should be radiolabeled with a radionuclide having high level of radiotoxic effectiveness such as Auger and/or alpha-emitter radionuclides. Iodine-125 and astatine-211 are very interesting radionuclides as being effective Auger and/or alpha-emitters. Briefly, the glucuronide prodrugs radiolabeled with iodine-125 or astatine-211 promise to be designed very effective anticancer agents in the future applications of cancer chemotherapy.

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Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer

Cited by 16 publications

References 19 publications

Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides

Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides

Radioiodine labeled CdSe/CdS quantum dots: Lectin targeted dual probes

Potential Use of Radiolabeled Glucuronide Prodrugs with Auger and/or Alpha Emitters in Combined Chemo- and Radio-Therapy of Cancer

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