For Patients With “Step Therapy” (generic before brand) ONLY: Based on review of available data, the Company may consider brand name non-steroidal anti-inflammatory drugs (NSAIDs), (including, but not limited to Celebrex ® [celecoxib], Voltaren Gel ® [diclofenac sodium], Motrin ® [ibuprofen], Mobic ® [meloxicam], Flector Patch ® [diclofenac epolamine], Pennsaid ® topical solution [diclofenac sodium], and Sprix ® nasal spray [ketoralac]) ‡ to be eligible for coverage when one of the below patient selection criteria is met:

[Non-steroidal anti-inflammatory drugs (NSAIDs)].

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

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1 4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020 There is an urgent need to identify effective drugs to fight against the virus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir;antidiabetic Amaryl;antibiotics Retapamulin, Rifimixin, and Rifabutin;antiemetic Fosaprepitant and Netupitant In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

Recent advancements in the development of heterocyclic anti-inflammatory agents.

A series of Bis-pyrazole Schiff bases (6a-d and 7a-d) and mono-pyrazole Schiff bases (8a-d and 9a-d) were designed and synthesized through the reaction of 5-aminopyrazoles 1a-d with aldehydes 2-5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) displayed MIC values (0.97-62.5 µg/mL) compared to Tetracycline (15.62-62.5 µg/mL) and Amphotericin B (15.62-31.25 µg/mL), MBC values (1.94-87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH2) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis, to determine the inhibitory activities with lower values in the case of DNA gyrase (8a and 9b) or nearly as DHFR compound 9b, while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases (8a and 9b) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b.

https://www.mdpi.com/1420-3049/25/11/2593/pdf

Discovery of New Schiff Bases Tethered Pyrazole Moiety: Design, Synthesis, Biological Evaluation, and Molecular Docking Study as Dual Targeting DHFR/DNA Gyrase Inhibitors with Immunomodulatory Activity.

New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Neurobehavioral investigation and acetylcholinesterase inhibitory activity study for some new coumarin derivatives.

Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study.

Lepidium meyenii or Maca is widely cultivated as a health care food supplement due to its nutritional and medicinal properties. Although there are a few in-depth studies evaluating Maca antihypertensive effects, the correlations between the chemical constituents and bioactivity of the plant have not been studied before. Thus, the roots were extracted using different solvents (aqueous, methanol, 50% methanol, and methylene chloride) and investigated for their antihypertensive and antioxidant activities through several in vitro assays. The methanolic extract exhibited the best renin and angiotensin converting enzyme (ACE) inhibitory activities with IC50 values of 24.79 ± 1.3 ng/mL and 22.02 ± 1.1 ng/mL, respectively, along with the highest antioxidant activity. In total, 120 metabolites from different classes, e.g., alkylamides, alkaloids, glucosinolates, organic acids, and hydantoin derivatives, were identified in the methanolic extract using ultrahigh-performance liquid chromatography/high-resolution mass spectrometry (UPLC/HRMS). Molecular docking simulations were used to investigate the potential binding modes and the intermolecular interactions of the identified compounds with ACE and renin active sites. Glucotropaeolin, β-carboline alkaloids, succinic acid, and 2,4-dihydroxy-3,5-cyclopentyl dienoic acid showed the highest affinity to target the ACE with high docking scores (S ranging from −35.32 to −22.51 kcal mol–1) compared to lisinopril (S = −36.64 kcal mol–1). Interestingly, macamides displayed the greatest binding affinity to the active site of renin with docking scores (S ranging from −22.47 to −28.25 kcal mol–1). Further, β-carbolines achieved docking scores comparable to that of the native ligand (S ranging from −13.50 to −20.06 kcal mol–1). Molecular dynamics simulations and MMPBSA were also carried out and confirmed the docking results. Additionally, the computational ADMET study predicted that the compounds attaining promising docking results had proper pharmacokinetics, drug-likeness characteristics, and safe toxicological profiles. Ultimately, our findings revealed that Maca roots could be considered a promising candidate as an antihypertensive drug.

https://pubs.acs.org/doi/pdf/10.1021/acsomega.2c01342

Rana H. Refaey

Papers

New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES

Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae.

Neurobehavioral investigation and acetylcholinesterase inhibitory activity study for some new coumarin derivatives.

Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study.

Lepidium meyenii (Maca) Roots: UPLC-HRMS, Molecular Docking, and Molecular Dynamics