AI Article Synopsis
- * Researchers designed two types of GPIIb/IIIa inhibitors: (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids, analyzing their interaction energies and effectiveness against platelet activation.
- * In animal studies, while both inhibitors could effectively reduce arterial thrombus formation, (1R,3S)-isomer showed superior efficacy and has greater potential for future modifications compared to (1S,3S)-isomer.
Article Abstract
In GPIIb/IIIa mediated arterial thrombosis platelet activation plays a central role. To discover platelet activation inhibitor the pharmacophores of GPIIb/IIIa receptor inhibitors and anti-thrombotic agents were analyzed. This led to the design of (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids as GPIIb/IIIa inhibitors. Comparing to (1S,3S)-isomer (1R,3S)-isomer had lower cdocker interaction energy. AFM image showed that the minimal effective concentration of (1S,3S)-isomer and (1R,3S)-isomer inhibiting platelet activation were 10 M and 10 M, respectively. In vivo 1 μmol/kg of oral (1S,3S)-isomer effectively inhibited the rats to form arterial thrombus and down regulated GPIIb/IIIa expression, but the activities were significantly lower than those of 1 μmol/kg of oral (1R,3S)-isomer. Both (1S,3S)-isomer and (1R,3S)-isomer can be safely used for structural modifications, but (1R,3S)-isomer should be superior to (1S,3S)-isomer.
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| http://dx.doi.org/10.1016/j.bmcl.2017.10.068 | DOI Listing |
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