A new analog of the active site of mononuclear dinitrosyl [1Fe–2S] proteins, [C3N2H8SFe(NO)2Cl][Fe(NO)2(C3N2H8S)2]+Cl− (I), has been synthesized by reacting NO with an aqueous mixture of iron(II) sulfate and N-ethylthiourea in acidic medium. The structure and properties of the complex were studied by X-ray diffraction, IR, Mössbauer, and EPR spectroscopy, in addition to quantum chemical calculations. Complex I spontaneously generates NO in protic media. The cytotoxicity of I was investigated against human cervical carcinoma (HeLa), breast cancer (MCF7), and non-immortalized (FetMCS) cell lines. The cytotoxicity of I against HeLa is similar to that of anticancer agents currently used clinically (platinum complexes), but I is 10 times less toxic in normal cells. The cytotoxicity of MCF7 cells to I is low.
A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.
We studied effects of NO-donor iron nitrosyl complex with N-ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the complex and underwent cell death after ETM exposure. The high susceptibility of A172 cells to ETM was attributed to its NO-donor properties since no toxicity was detected for the N-ethylthiourea ligand.