Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkers

Tiwari, Anand D.; Panda, Siva S.; Girgis, Adel S.; Sahu, Sandhyamayee; George, Riham F.; Srour, Aladdin M.; Starza, Brian La; Asiri, Abdullah M.; Hall, C. Dennis; Katritzky, Alan R.

doi:10.1039/c4ob01281j

Cited by 35 publications

(28 citation statements)

References 37 publications

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“…Nonsteroidal anti-inflammatory drugs (NSAIDs) that act on the affected tissues 3 , 4 by inhibiting the cyclooxygenase (COX) involved in the synthesis of prostaglandins are one of the major class of drugs used to treat inflammation. 5 − 9 …”

Section: Introductionmentioning

confidence: 99%

Pyridine- and Thiazole-Based Hydrazides with Promising Anti-inflammatory and Antimicrobial Activities along with Their In Silico Studies

et al. 2020

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A new class of compounds formed by the linkage of −C(O)–NH– with pyridine and thiazole moieties was designed, synthesized, and characterized by various spectral approaches. The newly characterized compounds were evaluated for their antimicrobial as well as anti-inflammatory properties. The in vitro anti-inflammatory activity of these compounds was evaluated by denaturation of the bovine serum albumin method and showed inhibition in the range of IC 50 values—46.29–100.60 μg/mL. Among all the tested compounds, compound 5l has the highest IC 50 value and compound 5g has the least IC 50 value. On the other hand, antimicrobial results revealed that compound 5j showed the lowest MIC values and compound 5a has the highest MIC values. Furthermore, molecular docking of the active compounds demonstrated a better docking score and interacted well with the target protein. Physicochemical parameters of the titled compounds were found suitable in the reference range only. The in silico molecular docking study revealed their COX-inhibitory action. Compound 5j emerged as a significant bioactive molecule among the synthesized analogues.

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Section: Introductionmentioning

confidence: 99%

Pyridine- and Thiazole-Based Hydrazides with Promising Anti-inflammatory and Antimicrobial Activities along with Their In Silico Studies

et al. 2020

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“…We have shown previously that conjugation of NSAIDs to paracetamol and anti‐ulcer drugs can be achieved through an amino acid linker to afford potential pro‐drugs. In addition, certain of these paracetamol–NSAID conjugates showed improved activity relative to the parent NSAID (Katritzky, Jishkariani, et al., 2009; Sahu et al., 2013; Tiwari et al., 2014). We therefore extended this chemistry to the conjugation of glucosamine with various NSAIDs.…”

Section: Resultsmentioning

confidence: 99%

Molecular docking‐guided synthesis of NSAID–glucosamine bioconjugates and their evaluation as COX‐1/COX‐2 inhibitors with potentially reduced gastric toxicity

et al. 2021

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Non‐steroidal anti‐inflammatory drugs (NSAIDs) are a powerful class of inhibitors targeting two isoforms of the family of cyclooxygenase enzymes (COX‐1 and COX‐2). While NSAIDs are widely used in the management of pain, in particular as a treatment for osteo‐ and rheumatoid arthritis, their long‐term use has been associated with numerous on‐ and off‐target effects. As the carboxylic acid moiety present in common NSAIDs is responsible for some of their adverse effects, but is not required for their anti‐inflammatory activity, we sought to mask this group through direct coupling to glucosamine, which is thought to prevent cartilage degradation. We report herein the conjugation of commonly prescribed NSAIDs to glucosamine hydrochloride and the use of molecular docking to show that addition of the carbohydrate moiety to the parent NSAID can enhance binding in the active site of COX‐2. In a preliminary, in vitro screening assay, the diclofenac‐glucosamine bioconjugate exhibited 10‐fold greater activity toward COX‐2, making it an ideal candidate for future in vivo studies. Furthermore, in an intriguing result, we observed that the mefenamic acid‐glucosamine bioconjugate displayed enhanced activity toward COX‐1 rather than COX‐2.

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“…Toxicological bioassay of the most promising vasodilatory active compounds ( 4a , c , e , f , g , l , m , r , s , t , w and 4x ) was determined using the standard reported method in mice [ 45 ]. Albino mice weighing 25–30 g were divided in 13 groups of 6 mice each.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators

et al. 2017

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A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a–x) was synthesized. All the new derivatives were examined via the standard technique for their vasodilation activity. Some of the investigated compounds exhibited a remarkable activity, with compounds 4w, 4e, 4r, 4s, 4f and 4g believed to be the most active hits in this study with IC50 values 0.223, 0.253, 0.254, 0.268, 0.267 and 0.275 mM, respectively, compared with amiodarone hydrochloride, the reference standard used (IC50 = 0.300 mM). CODESSA PRO was employed to obtain a statistically significant 2-Dimensional Quantitative Structure Activity Relationship (2D-QSAR) model describing the bioactivity of the newly synthesized analogs (N = 24, n = 4, R2 = 0.816, R2cvOO = 0.731, R2cvMO = 0.772, F = 21.103, s2 = 6.191 × 10−8).

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Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkers

Cited by 35 publications

References 37 publications

Pyridine- and Thiazole-Based Hydrazides with Promising Anti-inflammatory and Antimicrobial Activities along with Their In Silico Studies

Pyridine- and Thiazole-Based Hydrazides with Promising Anti-inflammatory and Antimicrobial Activities along with Their In Silico Studies

Molecular docking‐guided synthesis of NSAID–glucosamine bioconjugates and their evaluation as COX‐1/COX‐2 inhibitors with potentially reduced gastric toxicity

Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators

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