تاريخ مجلس الدراسات العليا

2022-08-18

اسم الطالب

محمد جاسم محمد

ملخص الرسالة

Due to the human glyoxalase I enzyme (Glo-I)'s overexpression in several carcinomas, including breast, colorectal, prostate, and bladder cancer, the Glo-I, a zinc metalloenzyme, is a crucial therapeutic target in the treatment of cancer. A lot of work has been put into finding and designing Glo-I enzyme competitive inhibitors as possible anticancer medicines. Here, a number of catechol derivatives were designed with the intention of creating novel Glo-I inhibitors. These compounds were then tested in vitro against the Glo-I enzyme and their structure-activity relationships (SARs) were examined to identify the key pharmacophore for Glo-I binding. With IC50 values in the low micromolar range, some substances demonstrated strong inhibitory action. Among the studied drugs, compound (64), with an IC50 value of 1.45 M, showed strong Glo-I inhibitory action. Compound 64's SAR analysis demonstrated the significance of the catechol moiety as well as the substituted location for catechol in the compound's inhibitory activity. The structural basis in agreement with the SARs analysis was validated by docking experiments, which investigated the binding mechanisms of all molecules in the active site. This investigation produced effective inhibitors that could be used as strong candidates for additional optimization to develop more effective Glo-I inhibitors.