Kimberly Shahi

Structural Consideration in Designing Organotin Polyethers to Arrest the Growth of Breast Cancer Cells In Vitro

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.

Antiviral Activity of Metal-Containing Polymers—Organotin and Cisplatin-Like Polymers

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.

Ability of Group IVB metallocene polyethers containing dienestrol to arrest the growth of selected cancer cell lines

BackgroundMonomeric Group IVB (Ti, Zr and Hf) metallocenes represent a new class of antitumor compounds. There is literature on the general biological activities of some organotin compounds. Unfortunately, there is little information with respect to the molecular level activity of these organotin compounds. We recently started focusing on the anti-cancer activity of organotin polymers that we had made for other purposes and as part of our platinum anti-cancer effort.MethodsFor this study, we synthesized a new series of metallocene-containing compounds coupling the metallocene unit with dienestrol, a synthetic, nonsteroidal estrogen. This is part of our effort to couple known moieties that offer antitumor activity with biologically active units hoping to increase the biological activity of the combination. The materials were confirmed to be polymeric using light scattering photometry and the structural repeat unit was verified employing matrix assisted laser desorption ionization mass spectrometry and infrared spectroscopy results.ResultsThe polymers demonstrated the ability to suppress the growth of a series of tumor cell lines originating from breast, colon, prostrate, and lung cancers at concentrations generally lower than those required for inhibition of cell growth by the commonly used antitumor drug cisplatin.ConclusionThese drugs show great promise in vitro against a number of cancer cell lines and due to their polymeric nature will most likely be less toxic than currently used metal-containing drugs such as cisplatin. These drugs also offer several addition positive aspects. First, the reactants are commercially available so that additional synthetic steps are not needed. Second, synthesis of the polymer is rapid, occurring within about 15 seconds. Third, the interfacial synthetic system is already industrially employed in the synthesis of aromatic nylons and polycarbonates. Thus, the ability to synthesize large amounts of the drugs is straight forward.

Influence of DMSO on the inhibition of various cancer cells by water-soluble organotin polyethers

The effect of solvent on the ability to inhibit a group of cell lines was studied employing a series of water-soluble dibutyltin polyethers derived from various hydroxyl-terminated poly(ethylene glycols). Molecular weight as a function of time was essentially unchanged for a period of 30 weeks for the polyethers. Variations in test media can affect biological activities on the cell level as well as at the molecular level. The current study involves the evaluation of the cellular effects when dimethyl sulfoxide (DMSO) is initially employed to dissolve the polymers compared with using water alone to dissolve the polymer. Even though caution was taken to employ DMSO at concentrations where cell interactions are not found for the control, differences were found between samples exposed to DMSO and those not exposed to DMSO. The general inhibition fingerprint is similar for both conditions but the particular EC50 results can vary 10-fold. Thus, the presence of DMSO does have some effect on the particular biolog...

Control of Prostate Cancer Using Organotin Polymers

The current efforts described in this paper are aimed at developing compounds that inhibit the growth of prostate cancer and to identify structure/property relationships that will further assist us towards this goal. The growth of prostate cancer is affected employing a wide range of organotin condensation polymers. The EC50 values are primarily dependant on the nature of the Lewis base but the CI50 is dependent on both the nature of the Lewis base and Lewis acid. EC50 values down to the picogram/mL range are found. A number of products exhibit CI50 values greater than two. For polymers derived from hydroquinone and hydroquinone derivatives ability to inhibit cancer cell growth decreases as the bulk of substituents increases.

Control of Breast Cancer Using Organotin Polymers

The efforts described in this article are aimed at designing organotin polymers that control the growth of breast cancer and to identify structure/property relationships that assist in this goal. The growth of MCF-7 and MDA-MB-231 breast cancer cell lines is inhibited employing a wide range of organotin condensation polymers. The EC50 values are primarily dependent on the nature of the Lewis base but the CI50 is dependent on both the nature of the Lewis base and Lewis acid. A number of products exhibit CI50 values greater than two including a number of organotin polyethers such as those derived from diethylstilbestrol, dienestrol, short-chained dibutyltin polyethers, and hydroquinone derivatives. In most of these cases the MDA-MB-231 cells exhibit greater inhibition compared to the estrogen receptor (ER) MCF-7 cells. The organotin polymers generally exhibit a superior ability to inhibit MCF-7 and MDA-MB-231 breast cell growth compared to the standard cisplatin. GRAPHICAL ABSTRACT

Control of colorectal cancer using organotin polymers

The efforts described in this paper are aimed at designing organotin polymers that control the growth of various cancers; here colorectal cancer and to identify structure/property relationships tha...