Optimization of labeled 125I- pyrimidine derivative and its biological evaluation

  • Authors

    • Atteyat Labib Qassim University
    2014-06-04
    https://doi.org/10.14419/ijbas.v3i3.2487

  • Abstract

    This study describe the organic synthesis of 2-iodobenzamido (2-N-nitrobenzen-5, 6, 7, 8 tetrahydrobenzothieno [2, 3-d]) pyrimidine -4-(3H) one as an example for some pyrimidine derivative used a new series of as potential cancer chemotherapeutic agents. The precursor derivative is ?-(2-iodobenzamido)-? - (4-nitrophenyl)-N- [3-ethoxy-carbonyl-4, 5, 6, 7-tetrahydrobenzothiophen-2-l] acrylic acid amide which react with hydrazine hydrate. The purification process was done via crystallization using solvent ethanol. The overall yield 78% the structure of the synthesized compound was confirmed by correct analytical and spectral data .Also, The synthesized compound was labeled with radioactive iodine -125 via nucleophilic substitution reaction ,in the presence cuprous chloride, the labeling process was carried out at 95oC for 60 min. the radiochemical yield was determined by using thin layer chromatography and the yield is equal to 80%.Preliminary in-vivo study was examined in normal mice were performed after intravenous injection through the tail vein and the data show the labeling compound was cleared quickly from most body organs. The radioiodinated compound showed high brain uptake .The results in this study suggest that radioiodinated pyrimidine derivative may be useful as cancer chemotherapeutic agents.

    Keywords: Pyrimidine Derivatives / Iodine -125/ Tissues Distribution.

  • References

    1. R Bairwa, N R Tawari, A Alate, S Anam, M S Degani, M Ray, R MG RajanNovel 2-hydrazino-pyrimidin-4 (3H)-one Derivatives with Pseudofunctional-Similarity to Siderophores as Potential Antimycobacterial Agents.Medicinal Chemistry 2013; 9 (1), 77-83
    2. Devani MB, Shishoo CJ, Pathak US, Parikh SH, Shah GF, Padhya AC. Synthesis of 3-substituted thieno[2,3-d]pyrimidin-4 (3H)-one-2-mercaptoacetic acids and their ethyl esters for pharmacological screening. Journal of Pharmaceutical Sciences. 1976;65(5):660-4.
    3. Dahiya R, Kumar A, Yadav R. Synthesis and Biological Activity of Peptide Derivatives of Iodoquinazolinones/Nitroimidazoles. Molecules. 2008;13(4):958-76.
    4. Katada J, Iijima K, Muramatsu M, Takami M, Yasuda E, Hayashi M, et al. Cytotoxic effects of NSL-1406, a new thienopyrimidine derivative, on leukocytes and osteoclasts. Bioorg Med Chem Lett. 1999;9(6):797-802.
    5. Amr AG, Mohamed AM, Mohamed SF, Abdel-Hafez NA, Hammam Ael F. Anticancer activities of some newly synthesized pyridine, pyrane, and pyrimidine derivatives. Bioorganic & medicinal chemistry. 2006;14(16):5481-8.
    6. Elansary A, Moneer A, Kadry H, Gedawy E. Synthesis and anticancer activity of some novel fused pyridine ring system. Arch Pharm Res. 2012;35(11):1909-17.
    7. Dai Y, Guo Y, Frey RR, Ji Z, Curtin ML, Ahmed AA, et al. Thienopyrimidine ureas as novel and potent multitargeted receptor tyrosine kinase inhibitors. Journal of medicinal chemistry. 2005;48(19):6066-83.
    8. Wang YD, Johnson S, Powell D, McGinnis JP, Miranda M, Rabindran SK. Inhibition of tumor cell proliferation by thieno[2,3-d]pyrimidin-4(1H)-one-based analogs. Bioorganic & medicinal chemistry letters. 2005;15(16):3763-6.
    9. Hopkins CR, Czekaj M, Kaye SS, Gao Z, Pribish J, Pauls H, et al. Design, synthesis, and biological activity of potent and selective inhibitors of mast cell tryptase. Bioorg Med Chem Lett. 2005;15(11):2734-7.
    10. Aboul-Fadl T, Radwan A, Attia M, Al-Dhfyan A, Abdel-Aziz H. Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative activity. Chemistry Central Journal. 2012;6(1):1-11.
    11. Amr Ael G, Abdel-Latif NA, Abdalla MM. Synthesis and antiandrogenic activity of some new 3-substituted androstano[17,16-c]-5'-aryl-pyrazoline and their derivatives. Bioorganic & medicinal chemistry. 2006;14(2):373-84.
    12. Amr Ael G, Sayed HH, Abdulla MM. Synthesis and reactions of some new substituted pyridine and pyrimidine derivatives as analgesic, anticonvulsant and antiparkinsonian agents. Archiv der Pharmazie. 2005;338(9):433-40.
    13. Amr AE-GE, Sherif MH, Assy MG, Al-Omar MA, Ragab I. Antiarrhythmic, serotonin antagonist and antianxiety activities of novel substituted thiophene derivatives synthesized from 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene-3-carboxamide. European Journal of Medicinal Chemistry. 2010;45(12):5935-42.
    14. Amr AG, Abdulla MM. Synthesis and anti-inflammatory activities of new cyanopyrane derivatives fused with steroidal nuclei. Archiv der Pharmazie. 2006;339(2):88-95.
    15. Farouk N, Ramadan HE, El-Amir MA. Labeling of EGFR inhibitor to prepare a potential SPECT agent for molecular imaging of breast cancer via iodine-bromine exchange. Radiochemistry. 2012;54(5):497-500.
    16. March J. March's advanced organic chemistry; reactions, mechanisms, and structure, 7th ed. Portland: Book News, Inc; 2013.
    17. Liu J, Wang B, Lin L, Zhang J, Liu W, Xie J, et al. Functional, physicochemical properties and structure of cross-linked oxidized maize starch. Food Hydrocolloids. 2014;36:45-52.
    18. Quitterer F, Beck P, Bacher A, Groll M. Structure and reaction mechanism of pyrrolysine synthase (PylD). Angewandte Chemie (International ed in English). 2013;52(27):7033.
    19. Zea-Ponce Y, Baldwin RM, Miliust RA, Bakthavachalam V, Innis RB. [123I]iodomethane, a main product in the synthesis of 5-[123I]iodo-6-nitroquipazine by iododestannylation. Journal of Labelled Compounds and Radiopharmaceuticals. 1995;36(4):331-7.
    20. El-Shahawi MS, El-Shaboury G, Aly MAM, El-Tawoosy M. Chemical and thermodynamic characteristics of the isotopic exchange reaction between radioiodine and iodohippuric acid isomers. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry. 2003;19(9):1331-4.
    21. El-Tawoosy M. Nucleophilic radioiodination of 6-bromocholesterol via non-isotopic exchange reaction in molten state. Journal of Radioanalytical and Nuclear Chemistry. 2001;249(3):535-40.
    22. El-Shaboury G, El-Tawousy M. Synthesis of radioiodinated 4-[I]iodoantipyrine via isotopic exchange. Journal of Radioanalytical and Nuclear Chemistry. 2002;252(1):109-14.

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  • How to Cite

    Labib, A. (2014). Optimization of labeled 125I- pyrimidine derivative and its biological evaluation. International Journal of Basic and Applied Sciences, 3(3), 160-165. https://doi.org/10.14419/ijbas.v3i3.2487

    Received date: 2014-04-18

    Accepted date: 2014-05-17

    Published date: 2014-06-04