Breast cancer is a major medical threat which cannot be sufficiently addressed by current therapies because of spontaneous or acquired treatment resistance. Besides, triple-negative breast cancer (TNBC) tumors do not respond to targeted therapies, thus new therapeutic strategies are needed. In this context, we designed and prepared new desulfured troglitazone (TGZ)-derived molecules and evaluated them in vitro for their anti-proliferative activity, with a special focus on triple-negative breast cancer cell lines. Optimization of the synthetic strategies and deracemization of the lead compound were performed to give highly active compound 10 with low-micromolar potency. Further studies revealed that this compound triggers apoptosis rather than cell cycle arrest as observed with TGZ.

In the field of organofluorine chemistry, the quest for emergent fluorinated groups is in high demand. In particular, the scientific community has shown special interest in the SCF3 residue thanks to its unique properties. Indeed, over the last decade, the SCF3 group has become a pivotal fluorinated moiety, as demonstrated by several SCF3-containing compounds of interest, and, related to that, the steadily increasing number of synthetic methods that are available to access such molecules. In this Short Review, the main advances made for the synthesis of trifluoromethylthiolated disubstituted alkenes will be discussed and highlighted.1 Introduction2 Trifluoromethylthiolation of Prefunctionalized Alkenes3 Direct C–H Trifluoromethylthiolation of Alkenes4 Trifluoromethylthiolation of Miscellaneous Derivatives5 Conclusion

Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ and AB186. Previous studies showed that both compounds induce apoptosis, nevertheless AB186 was a more potent agent. The kinetic of cellular events was investigated by real-time cell analysis system (RTCA) in MCF-7 (hormone dependent) and MDA-MB-231 (triple negative) breast cancer (TNBC) cells, followed by cell morphology analysis by immuno-localization. Both compounds induced a rapid modification of both impedance-based signals and cellular morphology. This process was associated with an inhibition of cell migration measured by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cells. In order to identify cytoplasmic targets of AB186, we performed surface plasmon resonance (SPR) and pull-down analyses. Subsequently, 6 cytoskeleton components were identified as potential targets. We further validated α-tubulin as one of the direct targets of AB186. In conclusion, our results suggested that AB186 could be promising to develop novel therapeutic strategies to treat aggressive forms of breast cancer such as TNBC.

By exploring an efficient and versatile method for the 6-functionalization of its scaffold, we investigated the opening of a new chemical space around benzylidenethiazolidine-2,4-dione (BTZD). The 6-chloro- and 6-formyl BTZD obtained in two steps starting from 5-lithioTZD were selected as key intermediates and involved in a Pd-catalyzed cross-coupling or Wittig olefination. A variety of aryl, heteroaryl, or alkenyl substituents was successfully introduced on the vinylic position of BTZD, and particular attention was paid to elucidate the stereochemistry of the benzylidene derivatives by using a combined DFT/NMR study.

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