Synthesis of 1',2'-O-isopropylidendioxyethyl isoxazoline derivatives of natural muscarinic analogs and screening its anti-cancer and leukocyte common antigen activity on Cdc25B and CD45 in vitro
10.16438/j.0513-4870.2017-1280
- VernacularTitle:天然蕈毒碱类似物1',2'-二-O-异亚丙基二氧乙基异噁唑啉衍生物的合成及其对Cdc25B和CD45体外抗癌和白细胞共同抗原活性筛选
- Author:
Mukhtar IMERHASAN
1
;
Setiwaldi HELIL
1
;
Ting WANG
1
Author Information
1. College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
1',2'-O-isopropylidendioxyethyl isoxazole;
synthesis;
in vitro anticancer activity;
leukocyte common antigen activity
- From:
Acta Pharmaceutica Sinica
2018;53(4):585-591
- CountryChina
- Language:Chinese
-
Abstract:
Muscimol, cycloserin and ibotenic acid which are extracted from mushroom contain isoxazole pharmacophore structure. By using muscarinic structure as a model compound and molecular recombination method, we synthesized muscarinic analogues compounds 3-(1',2'-di-O-isopropylidenedioxyethyl)-5-aryl-3a, 6a-dihydro-4,6-dioxopyrrolino[3',4'-d]isoxazoline derivatives through 1,3-dipolar cycloaddition reaction. The structures of the target compounds were confirmed by UV-Vis, 1H NMR, IR and elemental analysis. The drug activities of obtained compounds were screened in vitro. The pharmacophore in the structure is a potential non-covalent DNA binding, the compounds have anticancer activity and the leukocyte common antigen activity in a different extent. The preliminary results of in vitro anticancer test suggest that the inhibitory rates of compounds 3a-3o to Cdc25A phosphatase in cell division cycle ranged from 56.99%-99.94%; at the test concentration of 20 μg·mL-1, 3f, 3h, 3i, 3m, 3o were no inhibition activity, and the rest of the compounds shows moderate to good excellent inhibition rate from 66.85% to 99.84%, even at the concentration as low as 5 μg·mL-1. At the test concentration of 20 μg·mL-1, except compound 3i, the rest compounds' inhibition activity of against leukocyte common antigen (LCA) CD45 protein tyrosine phosphatase A, are 63.08%-92.09%. These active compounds are potential inhibitors against Cdc25A and CD45 protein tyrosine phosphatase A, which have great application prospects in the treatment of cancers and Inflammatory and immune diseases.
