Molecular Pharmacology, Vol 15, 341-356, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

The Antitumor Effects of Anthracyclines

The Importance of the Carbomethoxy-Group at Position-10 of Marcellomycin and Rudolfomycin

¹ Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030
² Bristol Laboratories, Syracuse, New York 13201

The effects of four anthracyclines on DNA, RNA and nucleolar RNA syntheses were compared to their in vitro cytotoxicity and in vivo antitumor activity. The results of these studies show that removal of the l0-carbomethoxy group from two class II anthracyclines, rudolfomycin and marcellomycin, resulted in a marked reduction in in vivo antitumor activity. The reduction in antitumor activity correlated with a loss of in vitro cytotoxicity, and a marked reduction in potency of nucleolar RNA synthesis inhibitory activity. This study supports the concept that a significant portion of the antitumor activity of class II anthracyclines is related to their ability to inhibit nucleolar RNA synthesis. These studies also demonstrate that the l0-carbomethoxy group is essential for nucleolar RNA synthesis inhibition by class II anthracyclines.

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ACKNOWLEDGMENTS The authors are indebted to Ms. Julie Durantini and Mrs. Polly Wischmeier for assistance in the preparation of this manuscript. We also thank Mrs. Clara Lartigue for her valuable technical assistance in the culturing and preparation of cells. The support and guidance of Dr. Harris Busch are most appreciated. The authors also wish to thank Dr. A. Prestayko and Dr. J. Strong for reviewing the manuscript.