Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Sharma, Vrinda; Bhatia, Parth; Alam, Ozair; Naim, Mohd. Javed; Nawaz, Farah; Sheikh, Aadil Ahmad; Jha, Mukund

doi:10.1016/j.bioorg.2019.103007

Cited by 97 publications

(63 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Celecoxib forms hydrogen bonds with COX-2 at Leu352, Ser353, and Phe513. We suggest that those hydrogen bonds could increase the binding affinity with COX-2, and that the modification of the SNAH dimethoxyphenyl ring might improve COX-2 inhibition because the substitution of methoxy group at para position was responsible for its high potency against COX-2 and high selective index [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

et al. 2020

View full text Add to dashboard Cite

We evaluated the anti-inflammatory effects of SNAH in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by performing nitric oxide (NO) assays, cytokine enzyme-linked immunosorbent assays, Western blotting, and real-time reverse transcription-polymerase chain reaction analysis. SNAH inhibited the production of NO (nitric oxide), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Additionally, 100 μM SNAH significantly inhibited total NO and ROS inhibitory activity by 93% (p < 0.001) and 34% (p < 0.05), respectively. Protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) stimulated by LPS were also decreased by SNAH. Moreover, SNAH significantly (p < 0.001) downregulated the TNF-α, IL-6, and iNOS mRNA expression upon LPS stimulation. In addition, 3–100 µM SNAH was not cytotoxic. Docking simulations and enzyme inhibitory assays with COX-2 revealed binding scores of −6.4 kcal/mol (IC50 = 47.8 μM) with SNAH compared to −11.1 kcal/mol (IC50 = 0.45 μM) with celecoxib, a known selective COX-2 inhibitor. Our results demonstrate that SNAH exerts anti-inflammatory effects via suppression of ROS and NO by COX-2 inhibition. Thus, SNAH may be useful as a pharmacological agent for treating inflammation-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, as a key player in tumorassociated inammation, COX-2 modulates radiation sensitivity, progression, and metastasis in a variety of cancers and leads to a reduction in overall survival. [1][2][3][4][5][6][7][8] A high 'molecular contrast' between healthy tissue and pathological lesions also forms the basis for successful radionuclide-based approaches. From the perspective of the oncologically oriented radiochemist/radiopharmacologist, COX-2 is a highly promising drugable target because (i) under physiological conditions it is nearly absent in tissues except kidneys, heart, and brain, (ii) its expression is inducible and COX-2 is overexpressed at inammatory sites and in (inamed) tumor tissue, and (iii) the availability of clinically approved drugs would allow the clinician to intervene in a personalized manner in, e.g., radioresistant tumors with high COX-2 expression.…”

Section: Introductionmentioning

confidence: 99%

Deuteration versus ethylation – strategies to improve the metabolic fate of an ¹⁸F-labeled celecoxib derivative

et al. 2020

View full text Add to dashboard Cite

show abstract

“…LMQC50 shows a pyrazole moiety, the same core as celecoxib ( Figure 1 and Figure 8 ), which favors a hydrogen bond interaction with h COX-2 ( Figure 5 B). Moreover, LMQC50 presents a 4-sulfonylmethylphenyl substitution at 1 position on the pyrazole ring which increases the inhibitory effects against COX-2 enzyme [ 84 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

et al. 2020

View full text Add to dashboard Cite

The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand.

show abstract

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cited by 97 publications

References 165 publications

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

Deuteration versus ethylation – strategies to improve the metabolic fate of an ¹⁸F-labeled celecoxib derivative

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

Contact Info

Product

Resources

About

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cited by 97 publications

References 165 publications

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

Deuteration versus ethylation – strategies to improve the metabolic fate of an 18F-labeled celecoxib derivative

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

Contact Info

Product

Resources

About

Deuteration versus ethylation – strategies to improve the metabolic fate of an ¹⁸F-labeled celecoxib derivative