Synthesis of new 3-(substituted-phenyl)-N-(2-hydroxy-2-(substituted-phenyl)ethyl)-N-methylthiophene-2-sulfonamide derivatives as antiproliferative agents

Abstract

In the present work, we report the synthesis of a series of 3-(substituted phenyl)-N-(2-hydroxy-2-(substituted-phenyl)ethyl)-N-methylthiophene-2-sulfonamide derivatives through Suzuki and Buchwald reaction. We have optimized methodology for targets from milligram to multi-gram scale. The newly synthesized compounds were characterized by ¹H NMR, ¹⁹F NMR, ¹³C NMR, LC-MS techniques and purity was further checked by HPLC. The compounds were evaluated for their in-vitro antiproliferative activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines by CCK-8 assay. The preliminary bioassay suggests that most of the compounds show antiproliferation with different degrees and 5-fluorouracil was used as positive control. Among these compounds 2d, 2g, 2i, 4e, 4h and 4k are most active compared to the standard. All the synthesized compounds show IC₅₀ values from 1.82-9.52 µM in different cell lines. Amongst these, compounds 2d, 2g, 2i, 4e, 4h and 4k were most potent, with IC₅₀ values ranging from 1.82-4.28 µM in different cell lines.