Novel thiazolo-pyrazolyl derivatives as xanthine oxidase inhibitors and free radical scavengers

Beedkar, Supriya D.; Khobragade, Chandrahasya N.; Chobe, Santosh S.; Dawane, Bhaskar S.; Yemul, Omprakash S.

doi:10.1016/j.ijbiomac.2012.02.009

Cited by 24 publications

(13 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A thiazole ring linked to two fused pyrazoles was the central skeleton of a library of 26 derivatives synthesized and tested in vitro by Beedkar et al . Compounds 133 (IC 50 =9 μ m ), 134 (IC 50 =7.1 μ m ), and 135 (IC 50 =6.5 μ m ) were reported to have IC 50 values similar to that of allopurinol.…”

Section: Non‐purine‐like Inhibitors Of Xosupporting

confidence: 86%

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

2019

View full text Add to dashboard Cite

Xanthine oxidase (XO) is the enzyme responsible for the catabolism of purines and their conversion into uric acid. XO is thus the target for the treatment of hyperuricemia and gout. For more than 50 years the only XO inhibitor drug available on the market was the purine analogue allopurinol. In the last decade there has been a resurgence in the search for new inhibitors of XO, as the activity of XO and hyperuricemia have also been associated with a variety of conditions such as diabetes, hypertension, and other cardiovascular diseases. In recent years the non‐purine inhibitor febuxostat was approved in Europe and the USA for the treatment of hyperuricemia. This drug was followed by another XO inhibitor called topiroxostat. This review discusses the molecular structures and activities of the multiple classes of inhibitors that have been developed since the discovery of allopurinol, with a brief review of the molecular interactions between inhibitors and XO active site residues for the most important molecules. The challenges ahead for the discovery of new inhibitors of XO with novel chemical structures are discussed.

show abstract

Section: Non‐purine‐like Inhibitors Of Xosupporting

confidence: 86%

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

2019

View full text Add to dashboard Cite

show abstract

“…In vitro XO inhibitory activity of compounds 5a–r was carried out spectrophotometrically by measuring uric acid levels at 295 nm (Table ) . Febuxostat was used as the reference drug.…”

Section: Resultsmentioning

confidence: 99%

“…DMSO (1% v/v) did not interfere with the enzyme activity. All the experiments were performed in triplicate and values were stated as mean of three experiments .…”

Section: Methodsmentioning

confidence: 99%

2‐Benzamido‐4‐methylthiazole‐5‐carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers

Ali

Kumar

Afzal

et al. 2017

Archiv der Pharmazie

View full text Add to dashboard Cite

The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2-benzamido-4-methylthiazole-5-carboxylic acid derivatives (5a-r) was synthesized and characterized by the collective use of IR, H and C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors.

show abstract

“…The docking of allopurinol and 19–21 was carried out at XO active site. Major lipophilic and ionic interactions included: Leu712 residue with compound 19 , Phe742, Phe798, Phe955 residues with compound 19 and 20 , and Ala910, Ala1079 residues with compound 21 …”

Section: Xanthine Oxidasementioning

confidence: 99%

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

show abstract

Novel thiazolo-pyrazolyl derivatives as xanthine oxidase inhibitors and free radical scavengers

Cited by 24 publications

References 44 publications

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

2‐Benzamido‐4‐methylthiazole‐5‐carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Contact Info

Product

Resources

About