Design, synthesis and in vitro evaluation of novel sulfonylurea and sulfonylthiourea as ectonucleotidases inhibitors

Herein, we describe the design, synthesis and biological evaluation of a series of novel non-nucleotide sulfonylurea and sulfonylthiourea based small molecule inhibitors of h-ENPP1, h-ENPP3 and e5′NT. Among the tested compounds, 3b inhibited h-ENPP1 with an IC50 value of 0.11 ± 0.01 µM. Similarly, 4b was found to be the most potent inhibitor tested against h-ENPP3 with an IC50 value of 0.038 ± 0.02 µM. Compound 3a revealed remarkable inhibitory potency against human ecto-5′-nucleotidase with an IC50 value of 0.83 ± 0.01 µM while compound 3b possessed IC50 value of 0.26 ± 0.05 µM against rat ecto-5′-nucleotidase. Antiproliferative activity of novel sulfonylurea and sulfonylthiourea derivatives was investigated on breast cancer cell line (MCF-7). Compound 4a showed anticancer activity against MCF-7 cell line with percentage inhibition of 64 and successfully arrested the viability of cancer cells. The compounds were not cytotoxic to the normal cells derived from baby hamster kidney (BHK-21).