Anticancer activity of functional polysuccinates with N-acetyl-cysteine in side chains.

The synthesis and characteristics of functional polyesters with a potential anticancer activity have been described, followed by a post-modification process of biologically active polymers. First, biodegradable functional polysuccinates possessing pendant allyl groups, that are susceptible to thiol-ene reaction, were obtained by polyaddition of succinic anhydride and allyl glycidyl ether. The functionality of such polyesters was regulated by replacing a part of unsaturated glycidyl ether with saturated ones. Polymers containing 20-100% mers with allyl groups were reacted with N-acetyl-cysteine (NAC). The use of simple click reaction allowed obtaining polyesters containing different amounts of N-acetyl-cysteine in side chains. The thus obtained polymers with a molecular weight of several thousand are characterized by solubility in methanol as opposed to their initial precursors. Modified polyesters show no toxicity to normal human keratinocytes (HaCaT) cells, similar to the NAC in normal human fibroblasts (NHDF), whereas the anticancer activities were observed against squamous carcinoma (SCC-25), and melanoma (Me45) cells. A standard colorimetric assay (MTS), to assessing cells viability and cytotoxicity of tested compounds, was performed against NHDF for NAC, HaCaT, SCC-25, and Me45 cells, within 24-144 h long-term expositions. Neither contact with NAC alone, and tested materials, nor long incubation decreased normal cell viability or induced inflammation. That reassumed the potential of anticancer activities of tested materials, with the tendency to visible selectivity against cancer cell lines in vitro, confirmed with live microscopic imaging against the Me45 cell line.