Synthesis and characterization of new types of halogenated and alkylated imidazolidineiminothiones and a comparative study of their antitumor, antibacterial, and antifungal activities.

摘要

A series of twenty novel imidazolidineiminothiones (4-8) with various substituents at N-(1) and N-(3) were synthesized by various permutations of halogenated and alkylated N-arylcyanothioformanilides (1) with aromatic isocyanates (2). Preliminary screening of all compounds against Ehrlich ascites carcinoma cells (EAC) indicated that 5d, and 8a-c were the most active compounds as they displayed the highest percent inhibition of cell viability (80%, 70%, 80%, and 70%, respectively). Thus, they were further subjected to in vitro biological evaluation against other tumor cancer cell lines (HEPG2, HEP2, MCF7, HELA, and HCT116). The IC50 values ranged from 3.12 to 12.1 mug/mL where compound 8b (N-(1): 2,4-dimethoxyphenyl; N-(3): 4-methoxyphenyl) was markedly active against all cell lines and consistently produced low IC50 values in all cases (ranging from 3.12 to 4.34 mug/mL). This underscored the synergistic effect of the suitably positioned methoxy groups on the aromatic rings of N-(1) and N-(3) of the imidazolidineiminothiones. All compounds were also tested against microbial organisms (Escherichia coli, Sarcina lutea, Bacillus subtilis, and Staphylococcus aureus), and fungal strains (Candida albicans and Aspergillus flavus). Most tested compounds showed significant activities which could be optimized with the appropriate selection of matching aromatic substituents on N-(1) and N-(3).