@inproceedings{01HRYQVVZKPX4HJMD4N03AA9A3,
  abstract     = {{Curcumin is a natural product, extracted from the rhizomes of the Curcuma longa plant, with a broad array of biological activities (antioxidant, anti-inflammatory, antimicrobial, anticancer…). With respect to its contribution to the field of cancer research, curcumin has been shown to affect different cellular signaling pathways and molecular targets involved in carcinogenesis, including apoptosis and inhibition of survival signals, reactive oxidative species (ROS) scavenging and reduction of the inflammatory cancer microenvironment. 
However, although cell culture assay results are promising, inferior efficacy of curcumin in clinical studies has been observed. Low solubility and absorption, as well as rapid metabolism lead to overall poor oral bioavailability, thereby impeding curcumin’s use as a therapeutic agent. Furthermore, several factors related to the structure of curcumin can provoke false positive results in biological assays as a consequence of interference with the assay readout rather than specific target interaction, making it a so-called pan-assay interference compound (“PAINS”). 
Profound structural modifications of the curcumin scaffold are thus necessary to progress toward a more suitable drug candidate. Previous research in our group has led to the discovery of two unprecedented benzothiazepane-based derivatives with promising anticancer activity, moving away from the traditional curcumin structure. The introduction of three-dimensionality (sp3 character) to the molecule improves properties related to drug-likeness, such as solubility and bioavailability. In addition, PAINS-activity attributed to sp2-based structural properties of the molecule could, in this way, be circumvented as well. 
Embarking on these findings, we recently developed a library of functionalized benzothiazepane systems to explore their biological activity in the context of cancer cell cytotoxicity. In particular, advanced synthesis efforts were made for the construction of a set of structural analogs of both hit molecules through modification of their different aromatic ring systems, involving the introduction of various carbo- and hetero-aromatics with varying substitution patterns and polarity. Ultimately, the anticancer cytotoxicity of nearly 30 new compounds was evaluated against a panel of eight cancer cell lines, which revealed useful and sometimes surprising understandings regarding their structure-activity relationship (SAR). In this presentation, we will discuss the chemistry developed to allow the synthesis of these new molecules and their biological properties in terms of anticancer cytotoxicity, followed by concluding SAR insights and prospects for future research.}},
  author       = {{Magdalenic, Katarina and Morlion, Felien and Ronse, Ulrike and De Jonghe, Steven and Persoons, Leentje and Schols, Dominique and De Munck, Julie and Grootaert, Charlotte and Van Camp, John and D'hooghe, Matthias}},
  booktitle    = {{4th Alpine Winter Conference on Medicinal and Synthetic Chemistry, Abstracts}},
  language     = {{eng}},
  location     = {{Sankt Anton am Arlberg, Austria}},
  title        = {{Curcumin as a source of inspiration for the development of novel benzothiazepane-based cancer cell cytotoxic agents}},
  year         = {{2024}},
}