Novel Conjugates of Aspirin with Phenolic Acid as Anti‐inflammatory Agents Having Significantly Reduced Gastrointestinal Toxicity

Jiang, Shan; Ding, Ning; Zhang, Wei; Zhang, Yichun; Geng, Meiyu; Li, Yingxia

doi:10.1002/ardp.200900217

Cited by 4 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a recent publication, Jiang et al reported a series of new conjugates of aspirin having one “phenolic acid antioxidant” group ( p -coumaric acid, ferulic acid, or caffeic acid) connected through a diol linker to the carboxylic acid group present in aspirin. These prodrugs showed considerable anti-inflammatory activity (croton oil-induced mice-ear swelling) without significant GI side-effects; one of the diol linkers used by Jiang’s group was tyrosol, which is the protecting group we used in this work to form NSAID esters, meaning that it is probably not essential to have the second (additional) phenolic acid antioxidants linked to tyrosol to maintain the anti-inflammatory profile of the corresponding NSAID or to decrease its ulcerogenic effects.…”

Section: Resultsmentioning

confidence: 99%

Nitric Oxide Release Is Not Required to Decrease the Ulcerogenic Profile of Nonsteroidal Anti-inflammatory Drugs

et al. 2012

View full text Add to dashboard Cite

The objective of this work was to evaluate the biological properties of a new series of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) possessing a tyrosol linker between the NSAID and the NO-releasing moiety (PROLI/NO); however, initial screening of ester intermediates without the PROLI/NO group showed the required (desirable) efficacy/safety ratio, which questioned the need for NO in the design. In this regard, NSAID ester intermediates were potent and selective COX-2 inhibitors in vitro, showed equipotent anti-inflammatory activity compared to the corresponding parent NSAID, but showed a markedly reduced gastric toxicity when administered orally. These results provide complementary evidence to challenge the currently accepted notion that hybrid NO-NSAIDs exert their cytoprotective effects by releasing NO. Results obtained in this work constitute a good body of evidence to initiate a debate about the future replacement of NSAID prodrugs for unprotected NSAIDs (possessing a free carboxylic acid group) currently in clinical use.

show abstract

Section: Resultsmentioning

confidence: 99%

Nitric Oxide Release Is Not Required to Decrease the Ulcerogenic Profile of Nonsteroidal Anti-inflammatory Drugs

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Still scientists have performed many experiments to obtain new different derivatives of ASA mostly to avoid aspirin-induced gastrointestinal effects including decreasing the acidity and increasing the pharmacological activity of the new designed aspirin-like drugs ( Khalikov et al, 2006 ; Jiang et al, 2010 ; Huang et al, 2012 ; Hussain et al, 2013 ). Recently, the new hydrophobic analogs of aspirin were developed showing inhibition of the production of pro-inflammatory and enrichment of anti-inflammatory cytokines ( Kalathil et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin

et al. 2016

View full text Add to dashboard Cite

The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3–300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however, it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-α level and mRNA expression were opposite. Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression. Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary.

show abstract

“…水杨酸作为重要有机原料中间体, 广泛用于医药、农药及食品添加剂的研究. 含水杨酸片段的化合物往往具有抑菌 [1] 、抗炎 [2] 、抗肿瘤 [3] 等多种生物活性. 近些年来, 该类衍生物在抗癌方面的研究逐渐增多, 如: 2011 年, Yamaguchi 等 [4] 研究发现通过水杨酸衍生物制备的前体药物 a 作为细胞凋亡诱导剂对肿瘤细胞有抑制作用, 尤其是对恶性黑色素瘤细胞效果显著; 2013 年, 王杰等 [5] 报道了水杨酰芳胺类化合物 b 对四种癌细胞 A-549, MCF-7, SGC-7901, Bel-7402 有不同程度的抑制活性; 2007 年, Gasco 等 [6] 报道 c 类衍生物对结肠癌、膀胱癌及前列腺癌有很好的治疗效果; Zhu 等 [7] 2010 年研究发现 d 系列衍生物可选择性作用于 VEGFR-2 亚型, 活性最好的化合物 IC 50 到达 3.8 nmol/L; 2009 年, Pickens 小组 [8] 发现天然活性物 e 中的水杨酸部分是该类物质抗癌的重要片段; 2011 年, Djurendić 等 [9] 自 1986 年, Giguere 研究小组报道微波在化学合成的应用以来, 微波辅助合成可加速反应并提高产率的研究不断增加, 在有机、药物合成领域的应用范围越来越广 [16,17] .…”

unclassified

Microwave-Assisted Synthesis and Antitumor Activity of Salicyl Acyloxy Phosphonate Derivatives

Yang¹,

Ma²,

Che³

et al. 2014

Chin. J. Org. Chem.

View full text Add to dashboard Cite

Novel Conjugates of Aspirin with Phenolic Acid as Anti‐inflammatory Agents Having Significantly Reduced Gastrointestinal Toxicity

Cited by 4 publications

References 26 publications

Nitric Oxide Release Is Not Required to Decrease the Ulcerogenic Profile of Nonsteroidal Anti-inflammatory Drugs

Nitric Oxide Release Is Not Required to Decrease the Ulcerogenic Profile of Nonsteroidal Anti-inflammatory Drugs

Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin

Microwave-Assisted Synthesis and Antitumor Activity of Salicyl Acyloxy Phosphonate Derivatives

Contact Info

Product

Resources

About