Synthesis, anti-inflammatory, cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide, oxime, and β-phenylalanine scaffolds: a molecular docking study

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

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Design, synthesis, anti-inflammatory assessment and molecular docking study of novel ketorolac analogues as potent anti-inflammatory agents targeting cyclooxygenase-2 enzyme

10.36295/asro.2020.232129 ◽

2020 ◽

Vol 23 (19) ◽

Author(s):

Farah AH. Kadhim ◽

Noor M. Mohammed ◽

Haider M. Badea Albadr

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Cyclooxygenase 2 ◽

Molecular Docking Study ◽

Design Synthesis ◽

Anti Inflammatory

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Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

Current Drug Therapy ◽

10.2174/1574885513666180503145352 ◽

2019 ◽

Vol 14 (1) ◽

pp. 85-90

Author(s):

Sagarika Biswas

Keyword(s):

Molecular Docking ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Docking Study ◽

Developed Countries ◽

Inhibitory Effect ◽

Molecular Docking Study ◽

Drug Designing ◽

Anti Inflammatory ◽

Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- α). Recent drug designing studies are developing TNF-α blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- α and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-α and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 µM inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-α in RA compared to control. Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-α mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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