New pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one hybrids linked to arene units: synthesis of potential MRSA, VRE, and COX-2 inhibitors

2021 ◽  
pp. 1-10
Author(s):  
Sherif M.H. Sanad ◽  
Ahmed E.M. Mekky
Keyword(s):  
Ternary Mixture ◽  
Inhibitory Concentration ◽  
Comparable Efficacy ◽  
Pyridine Moiety ◽  
Aryl Amines ◽  
Cox 2 ◽  
Mrsa Strains ◽  
Potential Inhibitors ◽  
Cox 2 Inhibitors ◽  
Tandem Synthesis

In the current study, we reported the tandem synthesis of two series of arene-linked pyrimidinone hybrids with related fused thieno[2,3-b]pyridine moiety. The target hybrids were prepared, in moderate to excellent yields, by the reaction of a ternary mixture of the appropriate of 3-aminothieno[2,3-b]pyridine-2-carboxylate, DMF-DMA, and a series of aryl amines in dioxane at 110 °C for 8 h. The antibacterial activity of the new hybrids was estimated against six susceptible ATCC strains. Hybrids 5g and 7g, linked to a sulfonamide unit, showed the best efficacy against S. aureus and E. faecalis strains with minimum inhibitory concentration (MIC) values of 1.7–1.8 μM, which exceed ciprofloxacin. Furthermore, some of new hybrids were examined as potential inhibitors of four different MRSA and VRE strains. Hybrids 5g and 7g demonstrated more potent efficacy than linezolid against MRSA strains with MIC values of 3.6/3.4 and 1.8/1.7 μM against ATCC:33591 and ATCC:43300 strains, respectively. The prior hybrids displayed a comparable efficacy with linezolid against VRE strains with MIC values of 7.3/6.9 and 3.6/3.4 μM against ATCC:51299 and ATCC:51575 strains, respectively. Additionally, some of the new hybrids were examined as potential COX-2 inhibitors using the reference celecoxib (IC50 of 0.117 µM). Hybrid 7g revealed more potent inhibitory efficacy than celecoxib with IC50 of 0.112 µM, whereas hybrid 5g showed almost inhibitory activity equivalent to celecoxib with IC50 of 0.121 µM. Molecular docking was performed to predict the possible binding interactions between hybrids 5g and 7g with the target COX-2 enzyme.

Pathophysiology and First-Line Treatment of Osteoarthritis

2002 ◽  
Vol 36 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jesse H Hogue ◽  
Tracey L Mersfelder
Keyword(s):  
Data Extraction ◽  
Treatment Options ◽  
Primary Treatment ◽  
Data Sources ◽  
Treatment Modalities ◽  
Comparable Efficacy ◽  
Antiinflammatory Drugs ◽  
Medline Search ◽  
Cox 2 ◽  
Cox 2 Inhibitors

OBJECTIVE: To review the pathophysiology of osteoarthritis (OA) and the various treatment modalities, focusing specifically on acetaminophen (APAP), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors as the primary treatment options. DATA SOURCES: Primary literature and tertiary references were identified by a MEDLINE search (1966–March 2001) and through other secondary sources. STUDY SELECTION AND DATA EXTRACTION: After evaluating the articles and references identified from the data sources, all the information that was judged relevant by the reviewers was included in the review article. DATA SYNTHESIS: OA is the most common joint disorder worldwide. Current research suggests that factors such as inflammation and changes in subchondral bone may play a larger role in the pathophysiology than previously thought. With this research and the development of COX-2 inhibitors, selecting the medication of choice for OA has become difficult. CONCLUSIONS: More research needs to be done before the pathophysiology of OA can be clearly determined. In the meantime, treatment should be based on clinical data and patient response. Studies have shown that APAP and NSAIDs have comparable efficacy, as do traditional NSAIDs and COX-2 inhibitors. APAP is associated with fewer toxicities than are the traditional NSAIDs. Due to their mechanism of action, the new COX-2 inhibitors should result in fewer adverse effects compared with traditional NSAIDs, but evidence from clinical trials has not been conclusive. Therefore, APAP should still be considered the drug of choice for OA.

Induction of gastric lesions by cyclooxygenase (COX-2) inhibitors in the stomach of adjuvant-induced arthritic rats

2001 ◽  
Vol 120 (5) ◽  
pp. A143-A144
Author(s):  
S KATO ◽  
Y OGAWA ◽  
T KUNIKATA ◽  
T WATANABE ◽  
T ARAKAWA ◽  
...  
Keyword(s):  
Gastric Lesions ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Synthesis and Evaluation of Benzimidazole Derivatives as Selective COX-2 Inhibitors

2015 ◽  
Vol 11 (2) ◽  
pp. 188-199 ◽  
Author(s):  
Ankita Rathore ◽  
Mujeeb-Ur-Rahman ◽  
Anees A. Siddiqui ◽  
Abuzer Ali ◽  
Mohammad Shahar Yar
Keyword(s):  
Benzimidazole Derivatives ◽  
Cox 2 ◽  
Cox 2 Inhibitors

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

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