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

Abstract

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.

Metallocene-containing polyesters from reaction of 3,5-pyridinedicarboxylic acid and metallocene dihalides and their preliminary ability to inhibit cancer cell growth

“…Cisplatin, among the most widely employed chemo-agent is included as a standard. Consistent with other studies done by us the metallocene monomers are relatively non-toxic [28,29,85,86] as is the Lewis base. Even so, the ability of various Group IVB metallocene small molecules to inhibit cancer growth is well established.…”

“…Bands assigned to the MÀO stretch in metallocene polyethers are generally assigned to about 440 for the asymmetric stretch and 345 for the symmetrical stretch. [28] These two bands are below the capability of the instrument employed in the present study. The asymmetric stretch for the MÀOÀC(O) group is identified as around 1150 and the corresponding symmetric stretch about 1070.…”

Sandwich Complex‐Containing Macromolecules: Property Tunability Through Versatile Synthesis

“…Like other macromolecules, sandwich complex‐containing macromolecules can be obtained through step polymerization mechanisms, which include esterification, hydrosilylation, amidation, and aromatic substitution, as well as other substitution reactions. These step polymerization reactions offer the opportunity to tune the properties of the sandwich complex‐containing macromolecule through the incorporation of various spacers . Electronics as well as the structure of the spacers tunes electronic interaction between the metal centers, solubility, and thermal properties of the resulting polymer.…”

“…Carraher and co‐workers synthesized several sandwich complex‐containing polymers by employing condensation reactions . For instance, a series of ferrocene‐containing organotin polyesters illustrated by 53 (Figure ) was obtained via the interfacial polycondensation reaction, which involved 1,1′‐ferrocenecarboxylic acid, sodium hydroxide, and various organotin dihalides .…”

Synthesis of organoarsenic, organoantimony, and organobismuth poly(ether esters) from reaction with glycyrrhetinic acid and their preliminary activity against pancreatic cancer cell lines

“…Included in the metal atoms incorporated into polymers are tin, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Group IVB metallocenes, [19][20][21][22][23][24][25][26][27][28][29][30] platinum, [31,32] and Group VA metals, namely arsenic, antimony, and bismuth. [33][34][35][36][37][38][39][40] Much of the most recent effort has focused on the special properties that can be incorporated into such polymers because of the presence of the metal moiety.…”