Roner, Michael R.

Organotin polyethers are easily synthesized employing interfacial
polymerization systems involving the reaction of hydroxyl-containing Lewis bases and
organotin halides. A wide variety of organotin-containing polymeric products have been
synthesized including those derived from natural and synthetic polymers such as lignin,
xylan, cellulose, dextran, and poly(vinyl alcohol). Others have been synthesized employing
known drug diols such as dicumarol, DES, and dienestrol and a wide variety of synthetic
diols. Included in these materials are the first water soluble organotin polymers. The
organotin polyethers exhibit a wide range of biological activities. Some selectively inhibit
a number of unwanted bacteria, including Staph. MRSA, and unwanted yeasts such as
Candida albicans. Some also inhibit a variety of viruses including those responsible for
herpes infections and smallpox. Others show good inhibition of a wide variety of cancer
cell lines including cell lines associated with ovarian, colon, lung, prostrate, pancreatic and
breast cancer. The synthesis, structural characterization, and biological characterization of
these materials is described in this review.

The ability to inhibit cancer is inherent in organotin materials yet the structural relationships that regulate/direct this activity remains unknown. We measured antitumor activity using a matched pair of cell lines MDA-MB-231 cells that are estrogen-independent, estrogen receptor negative and MCF-7 cells, a cell line that is estrogen receptor (ER) positive. Those polyethers that contained a O-phenyl unit were able to significantly inhibit the non-estrogen sensitive cell line but were much less effective against the estrogen sensitive cell line; that is, the human breast cancer cell line MDA-MB-231 showed better test results for polymers derived from diols containing the O-phenyl moiety than the breast cancer cell line MCF-7, a well-characterized estrogen receptor positive control cell line. Those polyethers that did not contain the O-phenyl unit inhibited both cell lines approximately the same. The differential activity of the O-phenyl-containing polyethers is likely due to the estrogen-sensitive cells combining with some of the organotin polyethers minimizing their ability to inhibit cell growth.

Polymers containing platinum and to a lesser extent tin, have repeatedly demonstrated antitumor activity in vitro and in vivo against a variety of cell and tumor types. The mechanisms responsible for the antitumor activity include inducing a delay in cell proliferation and sister chromatid exchanges blocking tumor growth. As most DNA and some RNA viruses require, and even induce, infected cells to initiate DNA replication and subsequent cell division, compounds with antitumor activity will very likely also possess antiviral activity. This article examines the use of metal-containing polymers as a novel class of antivirals.