Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition: synthesis, biological evaluation and docking studies

Kaur, Ramandeep; Naaz, Fatima; Sharma, Sahil; Mehndiratta, Samir; Gupta, Maneesh K.; Bedi, Preet Mohinder Singh; Nepali, Kunal

doi:10.1007/s00044-015-1382-0

Cited by 65 publications

(34 citation statements)

References 62 publications

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“…The pyran motif was also investigated by Nepali and colleagues with eight different libraries of compounds 197 – 204 . More than 100 compounds were synthesized and tested for inhibitory activity against XO at a concentration of 50 μ m .…”

Section: Non‐purine‐like Inhibitors Of Xomentioning

confidence: 99%

“…The R enantiomer of compound 196 was also found by molecular docking studies to fit better in the active site of the enzymethan its S enantiomer. The pyran motif wasa lso investigated by Nepali and colleagues [137] with eight different libraries of compounds 197-204.M ore than 100 compounds were synthesized and tested for inhibitory activity against XO at a concentration of 50 mm.O nly those compounds with more than 80 %i nhibitionw ere studied further.Atotal of 41 com-pounds met this condition, and werem easured to have IC 50 valuesr anging from 34.3 mm down to 0.59 mm for compound 205 (compared to allopurinol with IC 50 = 8.29 mm). SAR studies suggested that ah alogeno rn itro group was preferred over methoxy or hydroxy group as as ubstituent on the phenyl ring.…”

Section: Other Miscellaneous Compoundsmentioning

confidence: 99%

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

2019

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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.

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Section: Non‐purine‐like Inhibitors Of Xomentioning

confidence: 99%

Section: Other Miscellaneous Compoundsmentioning

confidence: 99%

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

2019

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“…The biological data (IC 50 ) of 4-aryl/ heteroaryl-4H-fused pyrans (Table 1) included in this study were obtained from literature 26 . IC 50 denotes the concentration of the test compound that exerts 50% inhibition of the biological action.…”

Section: Data Collectionmentioning

confidence: 99%

“…Recently, a series of forty-one 4-aryl/ heteroaryl-4H-fused pyrans, has been prepared and tested for xanthine oxidase (XO) inhibition 26 . This family of compounds offers great opportunity to identify the relevant properties inherent in these compounds that dictate their xanthine oxidase inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

Randic Shape and Size Indices Account for the Variability in Xanthine Oxidase Inhibitory Activity of a Family of Fused Pyrans

Billones¹,

Billones²

2017

Orient. J. Chem

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Gout and oxidative stress have been strongly associated with hyperuricemia, a metabolic defect marked by high levels of uric acid (UA) in the serum. Hyperuricemia has been managed by the use of drugs that inhibit xanthine oxidase. The recent account on synthesis of 4-aryl/heteroaryl-4H-fused pyrans as XO inhibitors provided excellent opportunity to uncover the crucial properties of these compounds that confer XO inhibitory action. In here, multiple linear regression analysis of DRAGON-type descriptors showed that the Randic Shape Index (PW3), and a size descriptor P_VSA_v_3account for the 75% of the variability of IC 50 values. Correlation studies with familiar QSAR descriptors indicate that the observed activity is primarily influenced by the molecular ovality and volume, and partly by charge distribution. The Comparative Molecular Field Analysis (CoMFA) models provide further insights on the steric and electronic features of this class of XO inhibitors.

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“…Pyranochromenone compounds have long been known to manifest a wide range of pharmaceutical properties, for instance, they exhibit anticancer, anti‐HIV, analgesic, anti‐inflammatory, anti‐TB, antifungal and cytotoxic activities (Figure ). Pyranochromenone derivatives act as xanthine oxidase inhibitor and also treat some neurodegenerative disorders, viz; Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Their existence in natural products is also significant ,…”

Section: Introductionmentioning

confidence: 99%

DABCO‐Catalysed One‐Pot Eco‐Friendly Synthetic Strategies for Accessing Pyranochromenone and Bis(benzochromenone) Compounds

et al. 2018

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An easy, facile and mild approach of liquid assisted grinding for the synthesis of novel dihydrobenzo[f]pyrano[3,2-c]chromenone derivatives using multicomponent cascade is herein described. The advantages of this protocol is one pot strategy, high reaction throughput, excellent yields, diversified scope, excellent score of green matrices. In addition, synthesis of bis (benzo[f]chromen-3-one) derivatives under microwave irradiation have also been established. The current methods utilize DABCO as a catalyst in forging these bioactive molecules. Also, all the final products are obtained by mere filtration, and the reaction conditions do not require any harsh reagents or typical work up.

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Screening of a library of 4-aryl/heteroaryl-4H-fused pyrans for xanthine oxidase inhibition: synthesis, biological evaluation and docking studies

Cited by 65 publications

References 62 publications

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

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

Randic Shape and Size Indices Account for the Variability in Xanthine Oxidase Inhibitory Activity of a Family of Fused Pyrans

DABCO‐Catalysed One‐Pot Eco‐Friendly Synthetic Strategies for Accessing Pyranochromenone and Bis(benzochromenone) Compounds

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