Design, synthesis and biological evaluation of N -pyridinyl ureidobenzenesulfonates and their hydrochloride salts as novel water-soluble dihydroorotate dehydrogenase inhibitors inducing differentiation of acute myeloid leukemia cells

= 12-31 nM). In addition, molecular docking studies show their stable binding modes in the brequinar-binding site of DHODH. Furthermore, PYRUB-SOs trigger the differentiation of a significant portion of the population of both MOLM-13 and THP-1 cells, as evidenced by increased CD11b single expression and increased CD11b and CD14 dual expression, respectively. Finally, they exhibit metabolic stability with half-lives varying from 57 to 216 min in rodent and human liver microsomes. Our study highlights that the new PYRUB-SO salts improve the water solubility of this new family of DHODH inhibitors while maintaining their biological activity.