Abstract
A series of 4-methoxyisophthalamides (1d–1w) were designed and synthesized and their chemical structures were confirmed by IR, MS, 1H-NMR, and 13C-NMR. The in vitro on anti-platelet aggregation activities of these compounds were assessed by using Born method. Compounds with higher activities were selected to continue research via Cell Counting Kit-8 (CCK-8) assays of their cytotoxicities. Biological screening results revealed four compounds 1h, 1i, 1q, and 1v exhibited higher activities than the control drugs on against the platelet aggregation induced by adenosine triphosphate (ADP). Moreover, compounds 1p and 1q exhibited higher in vitro activities than picotamide induced by collagen at the concentration of 1.3 μM. Compound 1p also possessed anti-platelet aggregation activity superior to the control drug picotamide induced by arachidonic acid (AA) at the concentration of 1.3 μM. At the same time, the result of cytotoxicities exhibited that none of the compounds have significant cytotoxicities. Therefore, 4-methoxyisophthalamides are potential to become novel anti-platelet drugs with high activities and minimum toxicities.
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Abbreviations
- ADP:
-
Adenosine triphosphate
- AA:
-
Arachidonic acid
- CCK-8:
-
Cell Counting Kit-8
- DMSO:
-
Dimethyl sulfoxide
- PAD:
-
Peripheral arterial disease
- PGI2 :
-
Prostaglandin I2
- SAR:
-
Structure activity relationship
- TLC:
-
Thin layer chromatography
- TXA2 :
-
Thromboxane A2.
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Acknowledgements
The authors are grateful to the National Science Foundation of China (11341014) & the Committee of Science and Technology of Tianjin of China (15JCZDJC33100) for the financial supports and Shenyang Pharmaceutical University of China for running platelet aggregation assays.
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Liu, X., Wang, Y., Liu, L. et al. Synthesis and in vitro activities on anti-platelet aggregation of 4-methoxyisophthalamides. Med Chem Res 27, 1971–1983 (2018). https://doi.org/10.1007/s00044-018-2207-8
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DOI: https://doi.org/10.1007/s00044-018-2207-8