@inproceedings{01J1A5RWP0YVBK54BKT70032ED,
  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 40 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 poster 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    = {{18th Belgian Organic Synthesis Symposium, Abstracts}},
  language     = {{eng}},
  location     = {{Liège, Belgium}},
  title        = {{Synthesis and anticancer activity assessment of curcumin-inspired benzothiazepane derivatives}},
  year         = {{2024}},
}