All-trans-retinoic acid (ATRA), the active metabolite of
vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective
therapy for dermatological disorders and
malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel
diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as
therapeutics for a variety of
cancers and
neurodegenerative diseases, including
amyotrophic lateral sclerosis. Here, we investigated the effects of these
retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by
ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10-6-10-5 M concentration range. All compounds induced
DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that
retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex
biological functions.