Synthesis, anticancer, and computational studies of 1, 3, <scp>4‐oxadiazole‐purine</scp> derivatives
Irum Shahzadi, Ameer Fawad Zahoor, Azhar Rasul, Nasır Rasool, Zohaib Raza, Shahla Faisal, Bushra Parveen, Shagufta Kamal, Muhammad Zia‐ur‐Rehman, Faisal Maqbool Zahid
Abstract
Abstract Theophylline‐7‐acetic acid (acefylline) ( 3 ) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of 2‐((5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1 H ‐purin‐7(6 H )‐yl)methyl)‐1,3,4‐oxadiazol‐2‐yl)thio)‐ N ‐arylacetamides ( 10a‐j ) has been reported. All the synthesized derivatives ( 10a‐j) were structurally verified by FT‐IR, 1 H NMR, 13 C NMR and evaluated for their anti‐cancer (using MTT assay), hemolytic and thrombolytic potential. N ‐(4‐Chlorophenyl)‐2‐(5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1 H ‐purin‐7(6 H )‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)acetamide ( 10g ) was found to be the most active against human liver cancer cell lines (Huh7) having cell viability 53.58 ± 1.28 using 100 μg/mL concentration of compound which was further in‐silico modelled to describe the possible mechanistic insights for its anti‐proliferative activity. The results of hemolytic and thrombolytic activities indicated that these derivatives were less toxic and hold considerable potential as a drug candidate. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1 H ‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐ N ‐(2‐fluorophenyl)acetamide ( 10c ) of the series was found to be least toxic with 0.1% hemolysis relative to ABTS (95.5%) as positive control. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1 H ‐purin‐7(6 H )‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐ N ‐(tetrahydro‐2 H ‐pyran‐4‐yl)acetamide ( 10j ) exhibited potent clot lysis activity (90%) as compared to negative control DMSO (0.57%).