Observations on the chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative

Abstract

This paper describes the preparation, chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative. Marycin has been prepared by condensing hematoporphyrin dimethyl ester in the presence of p-toluenesulfonic acid and reducing the product with lithium aluminum hydride. The product appeared to be pure by thin-layer chromatography (TLC) and high-performance liquid chormatography (HPLC). The product, analyzed by UV-visible absorbance and fluorescence spectra, appears to be related to the parent hematoporphyrin compound. The product was also analyzed by NMR and Mass spectra: a dimeric structure can be assigned to marycin: this appears to have an oxide bridge between C2-chains of two porphyrin units and hydroxyl groups instead of carboxyls. Marycin was screened for cytotoxic activity against ZR-75, MCF-7, HT-29, K-562, human tumor cell lines and the MRC-9 human embryonic cell line. Marycin decreases the growth index, measured in the radiometric assay, as 14CO2 production. The cytotoxic activity was dose-dependent and is attributable to the pure compound, marycin. Marycin is active at low doses but the activity varies with the cell line studied. The compound had low toxicity versus MRC-9 normal cell line. The compound is active without light activation. How marycin acts is a matter of speculation. Marycin is highly liposoluble and would be expected to have high toxicity for tumors.