Facile Synthesis and Radioiodine Labeling of Hypericin

Hypericin (1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione), an antidepressant which is also known to be a potent protein kinase C (PKC) inhibitor was synthesized as a precursor for radioiodine labeling via two step reactions. Malignant glioma cells express higher PKC activity compared to untransformed glial cell. Here we report the synthesis and radioiodine labeling of hypericin as a potential brain tumor imaging radiopharmaceutical. The reference compound, 2-iodohypericin, and its radiolabelled analogues, 2-[ 1 2 3 I]iodohypericin and 2-[ 1 2 4 I]iodohypericin have been prepared by the reaction of hypericin with Nal or [ 1 2 3 I]NaI or [ 1 2 4 I]NaI. The labeling yield was 60-65% for each analogue and the optimal reaction time was 10 min. The purification and isolation of the labelled products were achieved by a reversed-phase HPLC.

[1]  E. Gruszecka-Kowalik,et al.  AN IMPROVED SYNTHESIS OF HYPERICIN AND RELATED COMPOUNDS , 2000 .

[2]  R. Law,et al.  Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. , 1997, Cancer letters.

[3]  Z. Kovács,et al.  Excitation functions of 124Te(p, xn)124,123I reactions from 6 to 31 MeV with special reference to the production of 124I at a small cyclotron , 1995 .

[4]  Thomas C. Chen,et al.  Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines , 1994, FEBS letters.

[5]  J. Villemure,et al.  Protein Kinase C Inhibitors Suppress Cell Growth in Established and Low-Passage Glioma Cell Lines. A Comparison between Staurosporine and Tamoxifen , 1993 .

[6]  H. Falk,et al.  On the synthesis of hypericin by oxidative trimethylemodin anthrone and emodin anthrone dimerization: Isohypericin , 1992 .

[7]  J. Antel,et al.  Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C. , 1992, Neurosurgery.

[8]  S. Carpenter,et al.  Antiretroviral activity of synthetic hypericin and related analogs. , 1990, Biochemical and biophysical research communications.

[9]  M. Apuzzo,et al.  Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system. , 1990, Journal of neurosurgery.

[10]  I. Pollack,et al.  Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways. , 1990, Journal of neurosurgery.

[11]  I. Takahashi,et al.  Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. , 1989, Biochemical and biophysical research communications.

[12]  D. Weiner,et al.  Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Meruelo,et al.  Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Brockmann,et al.  Totalsynthese des Hypericins , 1957 .