Asymmetrically substituted cationic indole- and fluorene porphyrins inhibit tumor proliferation in small intestinal neuroendocrine tumors and medullary thyroid carcinomas.

Abstract

In this study we demonstrate anticancer activity of novel fully water soluble cationic porphyrins. The two cationic porphyrins 5,10,15-tris(N-methylpyridinium-4-yl)-20-[1-phenyl-4-(3-N-phenylsulfonylindolyl)]-21H,23H-porphyrin chloride (TMPy(3)PhenIndolprot(1)P-Cl(3)) and 5-{5-[2-(9,9-Dimethyl)fluorenyl]-N-methylpyridinium-3-yl}-10,15,20-tris(N-methyl-pyridinium-4-yl)-21H,23H-porphyrin chloride (TMPy(3)PyFluorenyl(1)P-Cl(4)) were prepared and their antiproliferative effects were studied in two human tumor cell lines and a normal human fibroblast cell line. Effects of the novel porphyrin compounds were evaluated in the small intestinal neuroendocrine tumor cell line KRJ-I, the medullary thyroid carcinoma cell line MTC-SK and the normal human fibroblast cell line HF-SAR by cell counting, cell proliferation assays and cell cytotoxicity analyses. TMPy(3)PhenIndolprot(1)P-Cl(3) and TMPy(3)PyFluorenyl(1)P-Cl(4) showed antiproliferative effects in the tumor cell lines MTC-SK and KRJ-I; cell viability was decreased and cytotoxic effects were quantified, while no significant alterations of the human fibroblasts were noted. With the advantage of full water solubility and antiproliferative effects in tumor cell lines, the novel porphyrin compounds TMPy(3)PhenIndolprot(1)P-Cl(3) and TMPy(3)PyFluorenyl(1)P-Cl(4) could be a new therapeutic option in anticancer treatment.

• Authors: Martin Haeubl, Susanne Schuerz, Bernhard Svejda, Lorenz Michael Reith, Bernadette Gruber, Roswitha Pfragner, Wolfgang Schoefberger
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 2 Pg. 760-73 (Feb 2010) ISSN: 1768-3254 [Electronic] France
• PMID: 19939515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Fluorenes
• Indoles
• Porphyrins
• Water
• fluorene
• DNA

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, metabolism, pharmacology)
• Base Sequence
• Cattle
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA (genetics, metabolism)
• Fluorenes (chemistry)
• Humans
• Indoles (chemistry)
• Neuroendocrine Tumors (drug therapy, pathology)
• Porphyrins (chemical synthesis, chemistry, metabolism, pharmacology)
• Solubility
• Thyroid Neoplasms (drug therapy, pathology)
• Water (chemistry)