Colon-targeting mutual prodrugs of 5-aminosalicylic acid and butyrate for the treatment of ulcerative colitis

Yan, Yan; Sun, Jing; Xie, Xianting; Wang, Pengchong; Ying, Sun; Dong, Yalin; Xing, Jianfeng

doi:10.1039/c7ra13011b

Cited by 18 publications

(13 citation statements)

References 34 publications

(41 reference statements)

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“…According to these physiological characteristics, traditional drug delivery systems based on colonic physiological characteristics, such as pH-dependent 17 , time-dependent 18 , and pressure-controlled 19 , have been proposed. In addition, passive targeting drug delivery systems initiated by microbial flora, such as enzyme-triggered 20 , prodrug delivery systems 21 , enzyme-degradable polymer-coated drug delivery systems 22 , and complex colon targeting drug delivery systems 23 , which combine several delivery systems, are used. In the field of drug carrier materials, chemical modification of carrier materials or carrier materials with strong sensitivity and specificity, stable drug release process, and nontoxic side effects is currently a research hotspot in this field.…”

Section: Advantages and Development Of Oral Colon-targeted Drug Delivmentioning

confidence: 99%

Design and application of oral colon administration system

Cheng

Huang

2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Oral colon administration system has become a new method to treat intestinal diseases. The implementation of colon drug delivery system is restricted by many aspects, including physical and chemical properties, drug delivery mode, gastrointestinal physiological factors, and so on. Delivery methods to overcome these challenges revolve around the mechanisms of drug delivery, including the use of rational dosage forms to avoid the complex pH environment, and the prevention of drug release and absorption in the upper digestive tract.

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Section: Advantages and Development Of Oral Colon-targeted Drug Delivmentioning

confidence: 99%

Design and application of oral colon administration system

Cheng

Huang

2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The in vitro release studies of all colon-targeted prodrugs 9 and 20a–20g were further carried out in a colon-content suspension (the colonic segment of the rat intestines was cut, and its contents were suspended to prepare the colon content suspension) at 37 °C from 0 to 5 h. ,− Sulfasalazine was used as a positive control to verify the activity of azo reductase in the colon content suspension (Figure A). Considering that the clinical studies showed that the oral therapeutic dose of olsalazine (colon-specific azo prodrug of 5-ASA) was much higher than that of tofacitinib (olsalazine and tofacitinib:1000 mg once daily and 5 mg twice daily, respectively), , the release exposures of 5-ASA from prodrugs were not tested in this study.…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA–PABA–MAC and 5-ASA–PABA–Diamine for the Treatment of Ulcerative Colitis

et al. 2022

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To mitigate the systemic adverse effects of tofacitinib, 5-ASA–PABA–MAC and 5-ASA–PABA–diamine colon-specific delivery systems were constructed, and tofacitinib azo prodrugs 9 and 20a–20g were synthesized accordingly. The release studies suggested that these systems could effectively release tofacitinib in vitro, and the 5-ASA–PABA–diamine system could successfully realize the colon targeting of tofacitinib in vivo. Specifically, compound 20g displayed a 3.67-fold decrease of plasma AUC(tofacitinib, 0–∞) and a 9.61-fold increase of colonic AUC(tofacitinib, 0–12h), compared with tofacitinib at a molar equivalent oral dose. Moreover, mouse models suggested that compound 20g (1.5 mg/kg) could achieve roughly the same efficacy against ulcerative colitis compared with tofacitinib (10 mg/kg) and did not impair natural killer cells. These results demonstrated the feasibility of compound 20g as an effective alternative to mitigate the systemic adverse effects of tofacitinib, and 5-ASA–PABA–MAC and 5-ASA–PABA–diamine systems were proven to be effective for colon-specific drug delivery.

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“…The 1 H and 13 C NMR spectra were recorded in d 6 DMSO. The 1 H NMR spectrum of the ligand exhibits two signals that appeared at 9.45 and 8.25 ppm belong to protons of COOH and phenolic OH groups, [ 35 ] respectively. The signal at 5.65 ppm corresponds to the –NH 2 protons.…”

Section: Resultsmentioning

confidence: 99%

“…that appeared at 9.45 and 8.25 ppm belong to protons of COOH and phenolic OH groups, [35] respectively. The signal at 5.65 ppm corresponds to the -NH 2 protons.…”

Section: H and 13 C Nmr Spectra Of The Ligandmentioning

confidence: 99%

Metal complexes of azo mesalamine drug: Synthesis, characterization, and their application as an inhibitor of pathogenic fungi

El-Sayed

Gaber

El-Wakeil

et al. 2021

Applied Organom Chemis

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A novel azo dye ligand, formed by the coupling of 5-aminosalycalic acid (mesalamine drug) with 2-amino pyrimidine (H 2 L) and its Co 2+ , Ni 2+ , and Cu 2 + complexes, was synthesized. The structures of ligand and its complexes have been described by elemental analysis, inductively coupled plasma (ICP), thermogravimetric analysis (TGA), magnetic moment measurements, molar conductance, ultraviolet-visible (UV-Vis), X-ray powder diffraction, infrared (IR), 1 H-nuclear magnetic resonance (NMR), 13 C NMR, and electron impact (EI) mass spectral studies. The obtained data detected that the H 2 L ligand acts as monobasic tridentate via C=N, azo nitrogen, and deprotonated OH groups. The data supported the formation of 1:2 (M:L) for Co 2+ complex, while Ni 2+ and Cu 2+ gave 1:1 (M:L) complexes mononuclear formulation. The Co 2+ and Ni 2+ complexes have octahedral structures, while Cu 2+ complex has tetrahedral geometry. The ligand and its Co 2+ , Ni 2+ , and Cu 2+ complexes were applied as an antifungal against a set of root rot-associated soil-born phytopathogenic fungi and compared with the effect of Hatric (recommended fungicide). Our findings revealed that the metal complexes exhibited greater antifungal activity than the parent ligand. The Cu 2+ complex was found to be the most effective compound.The effect of Hatric and Cu 2+ complex on structural alterations of Fusarium semitectum was studied by scanning electron microscopy (SEM).

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Colon-targeting mutual prodrugs of 5-aminosalicylic acid and butyrate for the treatment of ulcerative colitis

Abstract: The aim of this study was to design and synthesize four colon-targeting mutual prodrugs of 5-aminosalicylic acid (5-ASA) and butyrate, and evaluate their therapeutic effects on ulcerative colitis.

Cited by 18 publications

References 34 publications

Design and application of oral colon administration system

Design and application of oral colon administration system

Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA–PABA–MAC and 5-ASA–PABA–Diamine for the Treatment of Ulcerative Colitis

Metal complexes of azo mesalamine drug: Synthesis, characterization, and their application as an inhibitor of pathogenic fungi

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