Curcumin is recognized for its diverse biological activities, including the ability to induce apoptosis and ferroptosis. Therefore, it represents a promising candidate for the development of new compounds with neuroprotective and anticancer properties. In order to synthesize mimics with improved pharmacokinetic properties (better solubility and stability than curcumin) here, we present the design and synthesis of novel curcumin analogues named Ethylphosphonate-based curcumin mimics (EPs), which preserve the pharmacophoric features of curcumin. New EP mimics were synthesized by tyrosol- and melatonin-based building blocks using an orthogonal protection approach of the different precursors' OH functions with good yields and in a few steps. Comparative screenings of the cytotoxic and cytoprotective properties (curcumin was used as a reference compound) were carried out on all new mimics in different cell lines (HeLa, A375, WM266, MDA-MB-231, LX2, and HDF). Assays with inhibitors of ferroptosis (Ferrostatin-1, Fer-1) and apoptosis (Quinoline-Val-Asp-difluorophenoxymethyl ketone, Q-VD), in combination with curcumin, suggested the specific cell death pathway (apoptotic or ferroptotic) of EPs, depending on the aromatic moieties contained in them. Interestingly, EP4 exhibited substantial cytotoxic effects against various human cancer cell lines (HeLa, A375, WM266) while sparing normal cells (HDFs). EP4 displayed a five-times-higher toxicity in triple-negative MDA-MB-231 and LX2 stellate cells than curcumin. The cytotoxicity exerted by EP4 involves only an apoptotic mechanism, contrary to curcumin, which exerts both apoptotic and ferroptotic effects. Additionally, EP4 was also found to be a very potent inhibitor of the ubiquitin-activating enzyme E1, reinforcing the anticancer potential of this compound. Furthermore, EP2 possesses high antioxidant properties, efficiently protects against cell death by ferroptosis, and inhibits the amyloid aggregation involved in AD.

• Klíčová slova
• Alzheimer’s disease, apoptosis, cancer, curcumin mimics, ferroptosis, oxidative stress,
• Publikační typ
• časopisecké články MeSH

Cancer, an intricate and multifaceted disease, is characterized by the uncontrolled proliferation of cells that can lead to serious health complications and ultimately death. Conventional therapeutic strategies mainly target rapidly dividing cancer cells, but often indiscriminately harm healthy cells in the process. As a result, there is a growing interest in exploring novel therapies that are both effective and less toxic to normal cells. Herbs have long been used as natural remedies for various diseases and conditions. Some herbal compounds exhibit potent anti-cancer properties, making them potential candidates for nutraceutical-based treatments. However, despite their promising efficacy, there are considerable limitations in utilizing herbal preparations due to their poor solubility, low bioavailability, rapid metabolism and excretion, as well as potential interference with other medications. Nanotechnology offers a unique platform to overcome these challenges by encapsulating herbal compounds within nanoparticles. This approach not only increases solubility and stability but also enhances the cellular uptake of nutraceuticals, allowing for controlled and targeted delivery of therapeutic agents directly at tumor sites. By harnessing the power of nanotechnology-enabled therapy, this new frontier in cancer treatment presents an opportunity to minimize toxicity while maximizing efficacy. In conclusion, this manuscript provides compelling evidence for integrating nanotechnology with nutraceuticals derived from herbal sources to optimize cancer therapy outcomes. We explore the roadblocks associated with traditional herbal treatments and demonstrate how nanotechnology can help circumvent these issues, paving the way for safer and more effective cancer interventions in future oncological practice.

• Klíčová slova
• Nutraceuticals, bioavailability, cancer, herbal active compounds, nanotechnology,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Species of orchids, which belong to the largest family of flowering plants, are commonly used in folk medicine for the treatment of infections and tumors. However, little is known about the actual chemical composition of these plants and their anticancer properties. In this paper, the most recent literature on orchid-derived bioactive substances with anticancer properties is reviewed. For the assessment, previous papers on the anticancer activity of Orchidaceae published since 2015 were considered. The papers were found by exploring electronic databases. According to the available data, many species of orchids contain potential antitumor chemicals. The bioactive substances in a relatively insignificant number of orchids are identified, and most studies are on Asian taxa. Broader research on American and African species and the correct identification of samples included in the experiments are essential for evaluating the usefulness of orchids as a plant family with vast anticancer potential.

• Klíčová slova
• anticancer, orchids, secondary metabolites,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH