Synthesis, molecular docking, and pharmacological evaluation of <i>N</i>‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents

Kaur, Avneet; Pathak, Dharam Pal; Sharma, Vidushi; Wakode, Sharad

doi:10.1002/ardp.201800008

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…The test compounds displayed a high selectivity index for COX‐2 isoenzyme and presented a high in vivo efficacy in relieving carrageenan induced hyperalgesia in the animal models. The compound displayed a superior ADME profile thereby validating their utility as selective COX‐2 inhibitors (Kaur, Pathak, Sharma, & Wakode, 2018a; Kaur, Pathak, Sharma, & Wakode, 2018b). The compound with OCH 3 substituents at both the meta ‐positions displayed higher potency against COX‐2 isoenzyme and confers a markedly high selectivity index to the test compounds.…”

Section: Selective Cox‐2 Inhibitors Based On Azole Nucleusmentioning

confidence: 92%

“…The compound with OCH 3 substituents at both the meta ‐positions displayed higher potency against COX‐2 isoenzyme and confers a markedly high selectivity index to the test compounds. Interestingly, this compound displayed a superior tolerance toward the gastrointestinal mucosa compared to the standard drug ibuprofen (Kaur et al, 2018b). The benzoxazole based compounds 108a–c (Figure 17) provided preferential OX‐2 inhibitory profile with IC50 in the range 4.83–6.70 μM, and displayed significantly high molecular interactions with the residues lining the active site of COX‐2 isoenzyme.…”

Section: Selective Cox‐2 Inhibitors Based On Azole Nucleusmentioning

confidence: 99%

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“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Prasher

Sharma

2020

Drug Development Research

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An over‐expression of COX‐2 isoenzyme belonging to the Cyclooxygenase Enzyme Family triggers the overproduction of pro‐inflammatory prostaglandins that instigate the development of chronic inflammation and related disorders. Hence, the rationally designed drugs for mitigating over‐activity of COX‐2 isoenzyme play a regulatory role toward the alleviation of the progression of these disorders. However, a selective COX‐2 inhibition chemotherapy prompts several side effects that necessitate the identification of novel molecular scaffolds for deliberating state‐of‐the‐art drug designing strategies. The heterocyclic “azole” scaffold, being polar and hydrophilic, possesses remarkable physicochemical advantages for designing physiologically active molecules capable of interacting with a wide range of biological components, including enzymes, peptides, and metabolites. The substituted derivatives of azole nuclei enable a comprehensive SAR analysis for the appraisal of bioactive profile of the deliberated molecules for obtaining the rationally designed compounds with prominent activities. The comprehensive SAR analysis readily prompted the identification of Y‐shaped molecules and the eminence of bulkier group for COX‐2 selective inhibition. This review presents an epigrammatic collation of the pharmacophore‐profile of the chemotherapeutics based on azole motif for a selective targeting of the COX‐2 isoenzyme.

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Section: Selective Cox‐2 Inhibitors Based On Azole Nucleusmentioning

confidence: 92%

Section: Selective Cox‐2 Inhibitors Based On Azole Nucleusmentioning

confidence: 99%

“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Prasher

Sharma

2020

Drug Development Research

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“…We collected 259 COX-2 inhibitors from newly reported work − to build an external test set, which included 44 highly active inhibitors (IC 50 ≤ 0.1 μM) and 215 weakly active inhibitors (IC 50 ≥ 10 μM). All these 259 inhibitors were different from the 2925 inhibitors in data set 1.…”

Section: Materials and Methodsmentioning

confidence: 99%

Classification of Cyclooxygenase-2 Inhibitors Using Support Vector Machine and Random Forest Methods

Qin

Yang

Zhang

et al. 2019

J. Chem. Inf. Model.

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This work reports the classification study conducted on the biggest COX-2 inhibitor data set so far. Using 2925 diverse COX-2 inhibitors collected from 168 pieces of literature, we applied machine learning methods, support vector machine (SVM) and random forest (RF), to develop 12 classification models. The best SVM and RF models resulted in MCC values of 0.73 and 0.72, respectively. The 2925 COX-2 inhibitors were reduced to a data set of 1630 molecules by removing intermediately active inhibitors, and 12 new classification models were constructed, yielding MCC values above 0.72. The best MCC value of the external test set was predicted to be 0.68 by the RF model using ECFP_4 fingerprints. Moreover, the 2925 COX-2 inhibitors were clustered into eight subsets, and the structural features of each subset were investigated. We identified substructures important for activity including halogen, carboxyl, sulfonamide, and methanesulfonyl groups, as well as the aromatic nitrogen atoms. The models developed in this study could serve as useful tools for compound screening prior to lab tests.

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“…Kaur et al . synthesized a series of N -(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives and evaluated them for in vitro COX-I/II inhibitory activity.…”

Section: Recently Reported Cox Inhibitorsmentioning

confidence: 99%

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

et al. 2023

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Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in "housekeeping" roles, the expression of the COX-II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic antiinflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.

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Synthesis, molecular docking, and pharmacological evaluation of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents

Cited by 7 publications

References 39 publications

“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Classification of Cyclooxygenase-2 Inhibitors Using Support Vector Machine and Random Forest Methods

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective

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