engleski

Synthesis and Cytotoxic Evaluation of a New Ferrocene Triacyl Derivative of Resveratrol

Resveratrol (3, 5, 4′‐trihydroxy‐trans‐stilbene, RSV) is well known as a natural polyphenolic phytoalexin with a variety of biological benefits including antioxidant, anticancer, cardio- and neuroprotective, antimicrobial, antiviral, anti-inflammatory and other activities.1 With a view to overcoming drawbacks of resveratrol, such as low bioavailability and solubility, 2 and enhancing its biological potential, different structural modifications of the resveratrol have been made including modifications of hydroxyl groups, the presence of long alkyl chains or functionalized chains on the aromatic rings, conjugation etc.3, 4 Thereby, some of the prepared ferrocenyl-stilbene analogs with hidden phenolic function showed higher antitumor activity than resveratrol, most likely due to their lipophilicity and thus improved solubility in the cellular environment.4 In a continuation of our previous study on a ferrocene-resveratrol conjugates, 5 we have prepared resveratrol triester derivative I. The new compound (in concentrations 5 – 50µM) and RSV (in concentrations 2.5 – 100µM) have been tested for the possible cytotoxicity towards normal ovary cells (CHO-K1). After 48h of treatment with RSV, cell viability was significantly reduced determined with Neutral Red (in doses ≥50 µM) and MTT (in doses ≥10 µM) methods and dose-response pattern was clearly observed. Biological activity of resveratrol derivative I was notably modified compared to RSV, with new U-shaped dose-response curve (obtained with MTT method). Application of 50 µM compound I did not suppress cell viability (as observed with RSV), on the contrary – cell viability was induced which is confirmed by Neutral Red method. Flow cytometry also indicated lower cytotoxicity of derivative I vs. RSV. This work has been fully supported by Croatian Science Foundation under the project IP-2020-02-9162.

ferrocene-resveratrol conjugate, resveratrol, biological activity, ovary cells, apoptosis

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