Breast cancer is one of the leading causes of cancer death in women worldwide.[1] Among the various types of breast cancer, triple-negative breast cancers (TNBCs) are characterized by a lack of expression of estrogen and progesterone receptors and human epidermal growth factor 2 (HER2). They hence do not respond to targeted therapies and present a higher chance of recurrence after conventional chemotherapy treatments. In this context, thiazolidine-2,4-dione (TZD) derivatives which were shown to exhibit several biological activities are of particular interest.[2-6] Our team previously developed [7-9] Structure-Activity Relationships (SAR) starting from the structure of troglitazone (TGZ), formerly used as an antidiabetic. The present work was based on the synthesis of new desulfured troglitazone derivatives, and their in vitro biological evaluation on both TNBC and hormone-dependent breast cancer cell lines. [1] F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal, CA-Cancer J. Clin. 2018, 68, 394–424. [2] Mohd.J. Naim, Md.J. Alam, S. Ahmad, F. Nawaz, N. Shrivastava, M. Sahu, O. Alam Eur. J. Med. Chem. 2017, 129, 218–250. [3] Sucheta, S. Tahlan, P.K. Verma, Chem. Cent. J. 2017, 11, 130. [4] N. Chadha, M.S. Bahia, M. Kaur, O. Silakari, Bioorg. Med. Chem. 2015, 23, 2953–2974. [5] S. Prost, F. Relouzat, M. Spentchian, Y. Ouzegdouh, J. Saliba, G. Massonnet, J.-P. Beressi, E. Verhoeyen, V. Raggueneau, B. Maneglier, S. Castaigne, C. Chomienne, S. Chrétien, P. Rousselot, P. Leboulch, Nature 2015, 525, 380–383. [6] V. Shafiei‐Irannejad, N. Samadi, R. Salehi, B. Yousefi, N. Zarghami, Chem. Biol. Drug Des. 2017, 90, 1056–1066. [7] S. Salamone, C. Colin, I. Grillier-Vuissoz, S. Kuntz, S. Mazerbourg, S. Flament, H. Martin, L. Richert, Y. Chapleur, M. Boisbrun, Eur. J. Med. Chem. 2012, 51, 206–215. [8] A. Bordessa, C. Colin-Cassin, I. Grillier-Vuissoz, S. Kuntz, S. Mazerbourg, G. Husson, M. Vo, S. Flament, H. Martin, Y. Chapleur, M. Boisbrun, Eur. J. Med. Chem. 2014, 83, 129–140. [9] S. Mazerbourg, S. Kuntz, I. Grillier-Vuissoz, A. Berthe, M. Geoffroy, S. Flament, A. Bordessa, M. Boisbrun, Curr. Top. Med. Chem. 2016, 16, 2115–2124.