Abstract

USING ISOCYANATES IN SYNTHESIS OF IMIDAZOLIDINEIMINOTHIONE DERIVATIVES WITH EXPECTED APPLICATIONS IN MEDICINAL CHEMISTRY AND MOLECULAR DOCKING STUDY

Reem A. K. Al-Harbi* and Mona Alsharari

ABSTRACT

New imidazolidneiminothione derivatives have been synthesized through the cycloaddition reactions of selected isocyanates with various cyanothioformamide derivatives. The synthesized compounds were examined for their cytotoxic effects on three cancer cell lines HepG-2, HCT-116 and MCF-7. Most of compounds showed potency against cancer cell lines, among of them the dimethylaminophenyl derivatives showed strong results greater than the reference drug, where IC50 values of 4c were 7.32 μg/mL for HepG-2, 5.98 μg/mL for HCT-116, while the IC50 values of standard drug doxorubicin were 7.46, 8.29 respectively. Also, the synthesized compounds were screened for their antibacterial and antifungal activities, the dimethylaminophenyl derivatives 4a and 4c showed more potent effect than Metronidzole against A.niger. In-silico evaluations for all the synthesized compounds was undertaken in order to forecasting their ADME traits. In-silico molecular docking was also appraised for all the synthesized compounds on Phosphoinositide 3-kinase. The predictive in-silico results were in total agreement with the in-vitro outcomes, especially 4c acquired the highest docking score.

Keywords: Cycloaddition, Imidazolidneiminothione, Cyanothioformamide, Anti-cancer, Antifungal Antibacterial, In-silico molecular docking.