Evaluation of anti-leukemic activity of symmetrical 5-aminopyrazolyl disulfide derivatives

Three series of organosulfur compounds including 5-amino-4-thiopyrazole 2, 5-amino-4-(alkylthio)pyrazoles 3a-f, and symmetrical 5-aminopyrazolyl disulfide 4a-o were evaluated for anti-leukemic activity. These compounds were tested against four leukemia cell lines including Jurkat, HL-60, U937, and K562. Based on the in-vitro inhibitory results, most compounds 3a-f, and 4a-o exhibited significant inhibitory effects, particularly against Jurkat and HL-60 cells, with a more pronounced effect observed in Jurkat cells. Interestingly, several of compounds 4a-o possessed favorable inhibitory activity against U937 and K562. Their inhibitory activity was far superior to that of diallyl disulfide (DADS) and comparable to that of SNS-314. Further Western blot analyses of Hsp70 and Hsp90α expression, together with molecular simulation studies, revealed that compounds 4a exhibited favorable inhibitory profiles, including optimal structural alignment, suitable molecular interactions, and higher total interaction energies, comparable to the clinical agent SNS-314 and superior to the reference compound DADS. Based on these findings, compound 4a emerge as promising lead candidates for further development as potential antileukemic agents.