Resumen:
Several non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents in both pre-clinical and clinical studies on various cancer types. Here in, we developed several selenium (Se)-NSAID hybrid molecules and evaluated their efficacy as cancer therapeutics. The rationale for introducing Se into the NSAIDs is that this redox-active trace element is an essential micronutrient and a normal component of diets with chemopreventive and anticancer properties. Our recent studies have also shown that appropriately designed organoselenium compounds exhibited promising anti-tumor properties in various preclinical cancer models. We hypothesized that the rational incorporation of Se into NSAIDs should enhance their anti-cancer properties and therefore, we synthesized 16 novel Se-NSAID hybrid agents designed by incorporating Se moieties into the structures of aspirin, ibuprofen, and naproxen. In the first phase, a selenocyanate moiety was incorporated to these NSAIDs and screened for their cytotoxicity in various cancer cell lines. The cell viability results at 24 and 48 h showed that the introduction of this Se functionality on aspirin scaffold achieved a dramatic increase in the activity as compared to aspirin, as well as other NSAIDs or their Se hybrids. Thus, we continued optimization of aspirin with a variety of Se moieties, such as selenides and selenomethyl functionalities. Most of these compounds reduced cell viability in a dose dependent...
