Design, synthesis, biological and in silico evaluation of 3-carboxy-coumarin sulfonamides as potential antiproliferative agents targeting HDAC6 Suplementary Material

Breast cancer (BC) is the most common cancer and the main cause of mortality due to cancer in women around the World. Histone deacetylase 6 (HDAC6) is a promising target for the treatment of BC. In the present work, a series of novel 3-carboxy-coumarin sulfonamides, analogs of belinostat, targeting HDAC6 were designed and synthesized. These compounds were evaluated for their cytotoxic activity against the BC cell lines MCF-7 and MDA-MB-231 and the nonmalignant cells 3T3/NIH, where compounds 5, 8a-c exhibited antiproliferative activity comparable to that of cisplatin and doxorubicin. Molecular docking studies showed that compounds with the 3-benzoylcoumarin scaffold had good affinity with catalytic domain of HDAC6 and whose interactions are similar to those found in belinostat.Figure S 1 . 1 H NMR spectrum of compound 2 in CDCl 3 , 400 MHz. Figure S 2 . 13 C NMR spectrum of compound 2 in CDCl 3 , 100 MHz. Figure S 3 . 1 H NMR spectrum of compound 3 in DMSO-d6, 400 MHz. Figure S 4 . 13 C NMR spectrum of compound 3 in DMSO-d6, 100 MHz. Figure S 5 . 1 H NMR spectrum of compound 4a in DMSO-d6, 400 MHz. Figure S 6 . 1 H NMR spectrum of compound 4a in DMSO-d6. Figure S 7 . COSY spectrum of compound 4a in DMSO-d6. Figure S 8 . HSQC spectrum of compound 4a in DMSO-d6. Figure S 9 . HMBC spectrum of compound 4a in DMSO-d6. Figure S 10 . 1 H NMR spectrum of compound 4c in CDCl 3 , 400 MHz. Figure S 11 . 13 C NMR spectrum of compound 4c in CDCl 3 , 100 MHz. Figure S 12 . COSY spectrum of compound 4c in CDCl 3 . Figure S 13 . HSQC spectrum of compound 4c in CDCl 3 . Figure S 14 . HMBC spectrum of compound 4c in CDCl 3 . Figure S 15 . 1 H NMR spectrum of compound 5 in CDCl 3 , 400 MHz. Figure S 16 . 13 C NMR spectrum of compound 5 in CDCl 3 , 100 MHz. Figure S 17 . COSY spectrum of compound 5 in CDCl 3 . Figure S 18 . HSQC spectrum of compound 5 in CDCl 3 . Figure S 19 . 1 H NMR spectrum of compound 6 in CDCl 3 , 400 MHz. Figure S 20 . 13 C NMR spectrum of compound 6 in CDCl 3 , 100 MHz. Figure S 21 . 1 H NMR spectrum of compound 7 in DMSO-d6, 400 MHz. Figure S 22 . 13 C NMR spectrum of compound 7 in DMSO-d6, 100 MHz. Figure S 23 . 1 H NMR spectrum of compound 8a in DMSO-d6, 400 MHz. Figure S 24 . 13 C NMR spectrum of compound 8a in DMSO-d6, 100 MHz. Figure S 25 . COSY spectrum of compound 8a in DMSO-d6. Figure S 26 . HSQC spectrum of compound 8a in DMSO-d6. Figure S 27 . HMBC spectrum of compound 8a in DMSO-d6. Figure S 28 . 1 H NMR spectrum of compound 8b in DMSO-d6, 4