The position of the amino group on the benzene ring is critical for mesalamineʼs improvement of replication fidelity

Abstract

5-ASA shares its growth inhibitory and superoxide scavenging properties with its structural analogs and metabolite, but the position of the amino group is critical for reducing replication errors.

Systematic review: molecular chemoprevention of colorectal malignancy by mesalazine

“…This effect was shown to be independent of p53; however, p53 revealed strong phosphorylation at Ser15 residue upon exposure to 5‐ASA. Importantly, the position of the amino group in 5‐ASA benzene ring is critical for improvement of replication fidelity 21 . As p53 activates epidermal growth factor receptor (EGFR) expression in cancer cells 22 and EGFR function is required for cell cycle progression 23,24 there are many reasons to suggest a connection between 5‐ASA‐mediated phosphorylation of p53 and EGFR status.…”

Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases

“…At the cellular level 5-ASA reduces oxidative stress by inhibiting O 2 •− and H 2 O 2 production, as well as preventing mucosal GAPDH inhibition (Kimura et al 1998; Campregher et al 2010). Clinical trials indicated that in patients with UC, 4-week treatment with 5-ASA (2.4 g/day) plus N-acetyl- l -cysteine (0.8 g/day) not only improved clinical response but also correlated with decreased blood TNF-α, IL-6 and IL-8 concentration, as well as improved GSH content (Guijarro et al 2008).…”

“…in Fig. 1 ReferencePre-clinical studiesN-acetylocysteine↓MPO, ↑GSH in colon lesions↓iNOS in distal colon lesions↓MPO, ↑GSH, SOD, ↔ CAT in colon lesions↓COX-2, PGE2, nitrate concentration↓lipid peroxidation, ↑GSH, SOD in ulcerative colitis↓COX-2 and iNOS mRNA in colon lesions↓iNOS activity in UC↑GSH/GSSG ratio in intestinal subepithelial myofibroblasts in CD(5)(Nosal'ova et al 2000)(Seril et al 2002), (Cetinkaya et al 2005)(Ancha et al 2009)(Uraz et al 2013), (Nosal'ova et al 2000), (Cetinkaya et al 2005)(Ancha et al 2009)(Seril et al 2002), (Romagnoli et al 2012)Lipoic acid↑GSH, ↓MPO and lipid peroxidation in ileum and colon(5)(Kolgazi et al 2007)Curcumin and ellagic acid↓MPO, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS tissue level in CD(Baliga et al 2012), (Rosillo et al 2011)Tetradecylthioacetic acid↓iNOS, TNF-α and IL-6 mRNA in ulcerative colitis(Bjorndal et al 2013)Tributyrin↑TGF-β and IL-10 in lamina propria(Leonel et al 2012)Lactulose, a molecular hydrogen inducer↓TNF-α, IL-1β, MPO in colon lesions↓ONOO-, OH• in colonic lesions(3)(Chen et al 2013)(Ohsawa et al 2007)Ectoine↓IL-1α, IL-6, IL-8 and TNF-α(Sydlik et al 2009; Abdel-Aziz et al 2013)Clinical studiesMesalazine↓O2• − , H2O2 in UC↓IL-6, Il-8, ↔GSH, TNF-α in UC↑TNF-α, IL-1β and IL-6 in mucus of CD(7)(Campregher et al 2010)(Guijarro et al 2008)(Yamamoto et al 2009)Sulfasalazine↓ROS,↓IL-1β and IL-8 mRNA(Guo et al 2011)(Gan et al 2005)Glucocorticoids↓MPO and neutrophil elastase in paediatric IBD(Makitalo et al 2012)Cyclosporine↓IL-2, IL-3(Kountouras et al 2004)Infliximab↓TNF-α in colonic mucosa↓INF-γ mRNA in inflammatory cells in colitis(Fratila and...…”

Synthesis and in vitro Bioactivity Evaluation of New Galactose and Fructose Ester Derivatives of 5‐Aminosalicylic Acid

“…[1 -3] 5-Aminosalicylic acid (5-ASA) is one particular pharmaceutical that has long been favoured for the first-stage treatment of IBD because it causes relatively few side effects and is well tolerated by the majority of patients. [8] Up to the present time, diverse derivatives of this drug have been prepared to optimize the properties and applications of 5-ASA. [5] Experimental and epidemiological studies have revealed that, in long-term usage, 5-ASA represses gastrointestinal toxicity [1] and acts as a chemopreventive agent, [6][7] particularly against cancers of the intestine and colon.…”