ArticlesNo Access

Synthesis and toxicity of cobaltabisdicarbollide-containing porphyrins of high boron content

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA

Anhui Key Laboratory of Functional Molecular Solids and Anhui Key Laboratory of Molecular Based Materials, College of Chemistry and Material Science, Anhui Normal University, Wuhu, Anhui 241000, China

Search for more papers by this author

Xiaoke Hu

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA

Student member in good standing.

Search for more papers by this author

Frank R. Fronczek

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA

Search for more papers by this author

David G. Baker

Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA

Search for more papers by this author

Nobuko Wakamatsu

Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA

Search for more papers by this author

, and

M. Graça H. Vicente

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA

Corresponding author, tel: +1 225-578-7442.

SPP full member in good standing.

Search for more papers by this author

https://doi.org/10.1142/S1088424611003902Cited by:6 (Source: Crossref)

Abstract

Two porphyrins of high boron content (OCP and HCP–PEG) were prepared in high yields from the reaction of the corresponding tri- and tetra-(dihydroxyphenyl)porphyrins with zwitterionic cobaltabisdicarbollide [3,3′-Co(8-C₄H₈O₂-1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)]. Both porphyrins were found to have low cytotoxicity toward human HEp2 cells, and to localize subcellularly mainly in the cell lysosomes. Animal toxicity investigations using male and female BALB/c mice also revealed low toxicity for both compounds. The determined maximum tolerated dose (MTD) for these boronated porphyrins administered intraperitoneally were 160 mg/kg for OCP and 320 mg/kg for HCP–PEG. Our studies warrant further development of these porphyrins of high boron content, and in particular of HCP–PEG, as boron delivery vehicles for BNCT.

Dedicated to Professor Karl M. Kadish on the occasion of his 65^th birthday

Keywords:

References

a) Hawthorne MF. Angew. Chem. Int. Ed. Eng. 1993; 32: 950. b) Soloway AH, Tjarks W, Barnum BA, Rong FG, Barth RF, Codogni IM and Wilson JG. Chem. Rev. 1998; 98: 1515. c) Barth RF, Soloway AH, Goodman JH, Gahbauer RA, Gupta N, Blue TE, Yang WL and Tjarks W. Neurosurg. 1999; 44: 433 . Google Scholar
a) Barth RF, Coderre JA, Vicente MGH and Blue TE. Clinical Cancer Research 2005; 11: 3987. b) Sibrian-Vazquez M and Vicente MGH. In Boron Science: New Technologies & Applications, Hosmane NS. (Ed.) CRC Press: 2011; pp 203 . Google Scholar
R. F. Barth and H. Joensuu, Rad. Oncol. 82, 119 (2007), DOI: 10.1016/j.radonc.2007.01.010. Crossref, Web of Science, Google Scholar
M. G. H. Vicente and M. Sibrian-Vazquez, The Handbook of Porphyrin Science 4, eds. K. M. Kadish, K. M. Smith and R. Guilard (World Scientific Publishers, Singapore, 2010) p. 191. Link, Google Scholar
a) Hao E and Vicente MGH. Chem. Commun. 2005: 1306. b) Hao E, Jensen TJ, Courtney BH and Vicente MGH. Bioconjugate Chem. 2005; 16: 1495. c) Hao E, Sibrian-Vazquez M, Serem W, Garno JC, Fronczek FR and Vicente MGH. Chem. Eur. J. 2007; 13: 9035. d) Sibrian-Vazquez M, Hao E, Jensen TJ and Vicente MGH. Bioconjugate Chem. 2006; 17: 928. e) Hao E, Zhang M, E WB, Kadish KM, Fronczek FR, Courtney BH and Vicente MGH. Bioconjugate Chem. 2008; 19: 2171 . Google Scholar
a) Lindsey JS, Hsu HC and Schreiman IC. Tetrahedron Lett. 1986; 27: 4969. b) Lindsey JS and Schreiman IC. J. Org. Chem. 1987; 52: 827 . Google Scholar
M. Sibrian-Vazquez, T. J. Jensen and M. G. H. Vicente, J. Med. Chem. 51, 2915 (2008), DOI: 10.1021/jm701050j. Crossref, Web of Science, Google Scholar
M. Sibrian-Vazquezet al., Bioconjugate Chem. 16, 852 (2005), DOI: 10.1021/bc050057g. Crossref, Web of Science, Google Scholar
F. Teixidoret al., Organometallics 22, 3414 (2003), DOI: 10.1021/om030135o. Crossref, Web of Science, Google Scholar
J. H. Zhang, T. D. Chung and K. R. Oldenburg, J. Biomol. Screen. 4, 67 (1999), DOI: 10.1177/108705719900400206. Crossref, Web of Science, Google Scholar
a) Vicente MGH, Edwards BF, Shetty SJ, Hou Y and Boggan JE. Bioorg. Med. Chem.2002; 10: 481. b) Gottumukkala V, Luguya R, Fronczek FR and Vicente MGH. Bioorg. Med. Chem. 2005; 13: 1633. c) Gottumukkala V, Ongayi O, Baker DG, Lomax LG and Vicente MGH. Bioorg. Med. Chem. 2006; 14: 1871 . Google Scholar
a) Woodburn K, Phadke AS and Morgan AR. Bioorg. Med. Chem. Lett. 1993; 3: 2017. b) Nguyen T, Brownell GL, Holden SA and Teicher BA. Biochem. Pharm. 1993; 45: 147. c) Callahan DE, Forte TM, Afzal SMJ, Deen DF, Kahl SB, Bjornstad KA, Bauer WF and Blakely EA. Int. J. Rad. Oncol. Biol. Phys. 1999; 45: 761 . Google Scholar
a) Miura M, Micca PL, Fisher CD, Heinrichs JC, Donaldson JA, Finkel GC and Slatkin DN. Int. J. Cancer. 1996; 68: 114. b) Miura M, Micca PL, Fisher CD, Gordon CR, Heinrichs JC and Slatkin DN. Br. J. Radiol. 1998; 71: 773. c) Miura M, Micca PL, Heinrichs JC, Gabel D, Fairchild RG and Slatkin DN. Biochem. Pharmacol. 1992; 43: 467 . Google Scholar
M. G. H. Vicenteet al., Bioorg. Med. Chem. 11, 3101 (2003), DOI: 10.1016/S0968-0896(03)00240-2. Crossref, Web of Science, Google Scholar
a) Kahl SB, Joel DD, Nawrocky MM, Micca PL, Tran KP, Finkel GC and Slatkin DN. Proc. Natl. Acad. Sci. U.S.A. 1990; 87: 7265. b) Zhou R, Balasubramanian SV, Kahl SB and Straubinger RM. J. Pharm. Sci. 1999; 88: 912. c) Tibbitts J, Fike JR, Lamborn KR, Bollen AW and Kahl SB. Photochem. Photobiol. 1999; 69: 587 . Google Scholar
E. Haoet al., Org. Biomol. Chem. 20, 3732 (2008). Google Scholar
G. M. Sheldrick, Acta Crystallogr. Sect. A 64, 112 (2008), DOI: 10.1107/S0108767307043930. Crossref, Web of Science, Google Scholar
A. L. Spek, Acta Crystallogr. Sect. D-Biol. Crystallogr. 65, 148 (2009), DOI: 10.1107/S090744490804362X. Crossref, Web of Science, Google Scholar