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Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.

Zhen XE, Zong M, Gao SN, Cao YG, Jiang L, Chen SX, Wang K, Sun SQ, Peng HS, Bai YH, Li S - PLoS ONE (2014)

Bottom Line: The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa.The derivative was named Ca-ASP.Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.

ABSTRACT
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

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Related in: MedlinePlus

FTIR spectra of ASP and Ca-ASP.
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pone-0098513-g001: FTIR spectra of ASP and Ca-ASP.

Mentions: The corresponding FTIR spectrum of Aspirin and Hap-modified ASP (henceforth referred to as Ca-ASP) are shown in Figure 1 and their characteristic FTIR vibrations are listed in Table 1. For Aspirin, the main characteristic absorption peaks were clearly present, such as those at 1753(s) cm−1, 1690 cm−1 and 2500–3200 cm−1, which represent, respectively, acetyl group [C = O(CH3)], carboxylic acid group [νC = O(-COOH)] and hydroxyl group [18]. For Ca-ASP, anti-symmetric stretching vibration peak of νasCOO- shifted to lower wave number (from 1609 cm−1 to 1593 cm−1), while the symmetric stretching vibration peak of νsCOO- shifted to higher wave number (from 1419 cm−1 to 1444 cm−1), and the peak at 1690 cm−1 [νC = O(-COOH)] disappeared compared to the FTIR spectrum of ASP. This indicated the formation of a carboxylate [19]–[20]. On the other hand, the absorption peak of the carbonyl (acetyl) group [C = O(CH3)] in Ca-ASP also shifted to lower wave number (1753 to 1745 cm−1), and the absorption peak of hydroxyl (νOH) shifted to 3238 cm−1, indicating that a hydrogen bond was formed between the acetyl and hydroxyl groups [21]. Additional FTIR spectra were measured at 100°C and 200°C (data not shown), which indicated the strength and position of peak representing the acetyl group [C = O(CH3)] and hydroxyl (νOH) groups were not changed, and therefore the hydrogen bond between the acetyl group and the hydroxyl group was an intramolecular bond [22]. There were two new absorption peaks, one at 1033 cm−1 and the other at 567 cm−1, which were due to absorption by phosphate group. The analysis showed that Ca-ASP was derived from Hap, which formed a kind of carboxylate via reaction with ASP, resulting in the formation of an intramolecular hydrogen bond.


Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.

Zhen XE, Zong M, Gao SN, Cao YG, Jiang L, Chen SX, Wang K, Sun SQ, Peng HS, Bai YH, Li S - PLoS ONE (2014)

FTIR spectra of ASP and Ca-ASP.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043976&req=5

pone-0098513-g001: FTIR spectra of ASP and Ca-ASP.
Mentions: The corresponding FTIR spectrum of Aspirin and Hap-modified ASP (henceforth referred to as Ca-ASP) are shown in Figure 1 and their characteristic FTIR vibrations are listed in Table 1. For Aspirin, the main characteristic absorption peaks were clearly present, such as those at 1753(s) cm−1, 1690 cm−1 and 2500–3200 cm−1, which represent, respectively, acetyl group [C = O(CH3)], carboxylic acid group [νC = O(-COOH)] and hydroxyl group [18]. For Ca-ASP, anti-symmetric stretching vibration peak of νasCOO- shifted to lower wave number (from 1609 cm−1 to 1593 cm−1), while the symmetric stretching vibration peak of νsCOO- shifted to higher wave number (from 1419 cm−1 to 1444 cm−1), and the peak at 1690 cm−1 [νC = O(-COOH)] disappeared compared to the FTIR spectrum of ASP. This indicated the formation of a carboxylate [19]–[20]. On the other hand, the absorption peak of the carbonyl (acetyl) group [C = O(CH3)] in Ca-ASP also shifted to lower wave number (1753 to 1745 cm−1), and the absorption peak of hydroxyl (νOH) shifted to 3238 cm−1, indicating that a hydrogen bond was formed between the acetyl and hydroxyl groups [21]. Additional FTIR spectra were measured at 100°C and 200°C (data not shown), which indicated the strength and position of peak representing the acetyl group [C = O(CH3)] and hydroxyl (νOH) groups were not changed, and therefore the hydrogen bond between the acetyl group and the hydroxyl group was an intramolecular bond [22]. There were two new absorption peaks, one at 1033 cm−1 and the other at 567 cm−1, which were due to absorption by phosphate group. The analysis showed that Ca-ASP was derived from Hap, which formed a kind of carboxylate via reaction with ASP, resulting in the formation of an intramolecular hydrogen bond.

Bottom Line: The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa.The derivative was named Ca-ASP.Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.

ABSTRACT
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

Show MeSH
Related in: MedlinePlus