Acefylline Derivatives as a New Class of Anticancer Agents: Synthesis, Molecular Docking, and Anticancer, Hemolytic, and Thrombolytic Activities of Acefylline-Triazole Hybrids

Abstract

The synthesis of novel acefyllines and exploring their biological activities attract researchers due to their medicinal applications. Therefore, the current work reports the successful synthesis of a series of novel acefyllines in good yields, and their structures wereconfirmed using various spectroscopic methods. The synthesized acefyllines demonstrated moderate activity (cell viability = 22.55 ± 0.95% − 57.63 ± 3.65%) compared with the starting drug acefylline (cell viability = 80 ± 3.87%) against the human liver carcinoma (Hep G2 cell line). N-(4-Chlorophenyl)-2-(4-(3,4-dichlorophenyl)-5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-4H-1,2,4-triazol-3-ylthio)acetamide exhibited the most potent activity (cell viability = 22.55 ± 0.95%) among the synthesized derivatives. The in silico modeling studies were performed to predict the binding of the most potent derivative with a binding site that agreed with the results of the antiproliferative activity. The newly synthesized heterocycles exhibited the least hemolytic and moderate clot lysis activity.