چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| New compounds containing indanone and carbamate moieties were designed based on the hybrid pharmacophore approach. The designed compounds were synthesized and fully characterized by using different methods such as IR, Mass, 1H NMR, 13C NMR, and HPTLC. In vitro inhibitory activities of all synthesized compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The compound 3-[(5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl) methyl] phenyl (4-methoxyphenyl) carbamate (4h) showed the best inhibitory activities with IC50 values of 1.20 and 0.30 μM against AChE and BChE, respectively. In addition, this compound showed a β-amyloid self-aggregation inhibitory effect (86.8%), stronger than that of donepezil (45.5%). Moreover, significant neuroprotective activity on PC12 cells against H2O2 induced cell death was demonstrated for compound 4h at 10 and 100 μM concentrations. Kinetic studies using the 4h confirmed a partial non-competitive mixed type of inhibition mechanism on both enzymes. Considering the suggested inhibition mechanism, molecular docking was used to predict the possible allosteric binding mode of 4h with both AChE and BChE enzymes. The presented indanone-carbamate scaffold can be structurally modified and optimized through medicinal chemistrybased approaches for designing novel multi-target anti-Alzheimer agents. |
| نویسنده | نفر چندم مقاله |
|---|---|
| محمد شهریور گرگری | اول |
| مریم حمزه میوه رود | دوم |
| سالار همتی | سوم |
| جاوید شهبازی | چهارم |
| سیاوش دستمالچی | هشتم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| first paper in PhD course.pdf | 1400/09/28 | 3293255 | دانلود |
