Design, synthesis and biological evaluation of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid derivatives as novel xanthine oxidase inhibitors

Mao, Qing; Dai, Xiwen; Xu, Gaoyang; Su, Yu; Zhang, Bing; Liu, Dan

doi:10.1016/j.ejmech.2019.07.061

Cited by 35 publications

(28 citation statements)

References 47 publications

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“…In an acute oral toxicity study, this derivative did not lead to behavioral abnormality 24 h after the administration of a single dose of 2000 mg/kg, which suggested that the LD 50 value might be higher than 2000 mg/kg, being near 400 times over the effective dose (5 mg/kg) [22].…”

Section: Febuxostat Analoguesmentioning

confidence: 93%

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

Serrano

Figueiredo

Almeida

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Hyperuricemia is characterized by elevated uric acid (UA) levels on blood, which can lead to gout, a common pathology. These high UA levels are associated with increased purine ingestion and metabolization and/or its decreased excretion. In this field, xanthine oxidase (XO), by converting hypoxanthine and xanthine to UA, plays an important role in hyperuricemia control. Based on limitations and adverse effects associated with the use of allopurinol and febuxostat, the most known approved drugs with XO inhibitory effect, the search for new molecules with XO activity is growing. However, despite the high number of studies, it was found that the majority of tested products with relevant XO inhibition were left out, and no further pharmacological evaluation was performed. Thus, in the present review, available information published in the past six years concerning isolated molecules with in vitro XO inhibition complemented with cytotoxicity evaluation as well as other relevant studies, including in vivo hypouricemic effect, and pharmacokinetic/pharmacodynamic profile was compiled. Interestingly, the analysis of data collected demonstrated that molecules from natural sources or their mimetics and semisynthetic derivatives constitute the majority of compounds being explored at the moment by means of in vitro and in vivo animal studies. Therefore, several of these molecules can be useful as lead compounds and some of them can even have the potential to be considered in the future clinical candidates for the treatment of hyperuricemia.

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Section: Febuxostat Analoguesmentioning

confidence: 93%

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

Serrano

Figueiredo

Almeida

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…These pyrimidines and their scaffolds exhibit a broad spectrum of bioactivity; hence they occupy privileged positions in drug discovery studies. Dihydropyrimidine-5-carboxylic acid analogs 42 were synthesized and evaluated for their xanthine oxidase (XO) inhibitory activity [101]. All the tested molecules exhibited good XO inhibitory activity with IC50 values ranging from 0.018-0567 M.…”

Section: Pyrimidinesmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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“…Abnormal levels of this enzyme may cause hyperuricemia and gout. [30] Additionally, abnormal levels of the activity of XO is associated with different cancer types. [31] Therefore, it is highly important that the control of XO activity to prevent uric acid or reactive oxygen species caused health problems.…”

Section: Enzyme Inhibition Studiesmentioning

confidence: 99%

“…Thus, many research groups investigated different structures in order to develop non-purine XO inhibitors. [30] Inhibitory properties of some coumarin derivatives on the activity of XO were also reported, albeit rare. [32,33] After the achieved promising inhibitory activity on the hCA I and II isoenzymes, we decided to evaluate the XO inhibitory properties of CQACs.…”

Section: Enzyme Inhibition Studiesmentioning

confidence: 99%

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation

Karataş

Noma

Gürses

et al. 2020

Chemistry & Biodiversity

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In the present study, coumarin‐bearing three pyridinium and three tetra‐alkyl ammonium salts were synthesized. The compounds were fully characterized by 1H‐ and 13C‐NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco‐2) and non‐cancer mouse fibroblast (L‐929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.

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Design, synthesis and biological evaluation of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid derivatives as novel xanthine oxidase inhibitors

Cited by 35 publications

References 47 publications

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation

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