Design, Synthesis and Biological Screening of Aminoacetylenic Tetrahydrophthalimide Analogues as Novel Cyclooxygenase (Cox) Inhibitors

Basim, Ahmed; Eldeen, Zuhair A. Muhi; Al‐Kaissi, Elham; Suaifan, Ghadeer A. R. Y.; Ghattas, Mohammad A.; Arafat, Tawfeeq; Al-Adham, Ibrahim

doi:10.22159/ijpps.2017v9i2.15511

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…19 The Aryl group that could selectively differentiate between COX-1 and COX-2 inhibitory activity of aminoacetylenic analogues. 10,11,12 in our study we suggest that the removal of the acetylenic group in this study showed that it might be a different binding site in COXs which may result in effective compounds. there is no precise or specific pattern observed at COXs binding sites 23…”

Section: Chemistrymentioning

confidence: 59%

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Al-Husseini

Muhi-Eldeen

Al-Tameemi

et al. 2022

Int J Life Sci Pharm Res

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Inflammation is the vital part of the immune system's response to injury and infection. It is the body's way of signaling the immune system to heal and repair damaged tissue. The objective of this paper is to design and synthesize a new isoindoline 1,3-dinoe derivative and investigate their selective anti inflammatory activity to COXs. As a potential anti-inflammatory compound, Isoindoline-1,3-dione derivatives were synthesized from the addition reaction of phthalimide, formaldehyde, catalytic amount of potassium hydroxide and cyclic amine in ethanol yielded the desired Isoindoline-1,3-dione compounds (ZJ1-ZJ6. 1H- NMR, ¹³C-NMR, FT-IR and elemental analysis were consistent with the assigned structures. Isoindoline-1,3-dione derivatives exhibited good inhibitory activity against the COX enzymes. To explain the result of our investigation to COX-1 and COX-2 and the selectivity of our compounds to either COX-1 or COX-2, the rationalization in COX-1, the amino group participate more effectively in binding with the ligand while in COX-2, the aryl group is more effective in binding to the ligand. The amino acetylenic compounds behave differently toward COXs from our compound. ZJ4 have shown some selective COX-1 ligand efficiency while ZJ1 promised a potent blockage and ligand efficiency toward the COX-2 enzyme which was found to be higher than the marketed drug Indomethacin and near potency score of Celecoxib. For the first time, this indicates the requirement of investigating the removal of acetylenic group in this study showed that it might be a different binding site in COXs which may result in effective compounds.

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Section: Chemistrymentioning

confidence: 59%

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Al-Husseini

Muhi-Eldeen

Al-Tameemi

et al. 2022

Int J Life Sci Pharm Res

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show abstract

Section: Chemistrymentioning

confidence: 59%

“…9 As a part of our investigation for the structure relationship activity (SAR) for amino acetylenic isoindoline-1,3-dione as anti-inflammatory agent, in this paper; the acetylenic moiety was removed to generate isoindoline-1,3-dione derivatives of potential COXs inhibitors. 10,11,12 11 A mixture of Formaldehyde (39%, 30.1 mL), Heterocyclic amine e.g. 2,6 dimethylpiperidine (1.7 g, 0.01 mole) and 50ml ethanol was heated and stirred under reflux for 30 minutes at a temperature of 70ᵒC.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Jaafar¹,

Zuhair²,

Sadeq³

et al. 2021

Int J Pharma Bio Sci

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Inflammation is the vital part of the immune system's response to injury and infection. It is the body's way of signaling the immune system to heal and repair damaged tissue. The objective of this paper is to design and synthesize a new isoindoline 1,3-dinoe derivative and investigate their selective anti inflammatory activity to COXs. As a potential anti-inflammatory compound, Isoindoline-1,3-dione derivatives were synthesized from the addition reaction of phthalimide, formaldehyde, catalytic amount of potassium hydroxide and cyclic amine in ethanol yielded the desired Isoindoline-1,3-dione compounds (ZJ1-ZJ6. 1H-NMR, ¹³C-NMR, FT-IR and elemental analysis were consistent with the assigned structures. Isoindoline-1,3-dione derivatives exhibited good inhibitory activity against the COX enzymes. To explain the result of our investigation to COX-1 and COX-2 and the selectivity of our compounds to either COX-1 or COX-2, the rationalization in COX-1, the amino group participate more effectively in binding with the ligand while in COX-2, the aryl group is more effective in binding to the ligand. The amino acetylenic compounds behave differently toward COXs from our compound. ZJ4 have shown some selective COX-1 ligand efficiency while ZJ1 promised a potent blockage and ligand efficiency toward the COX-2 enzyme which was found to be higher than the marketed drug Indomethacin and near potency score of Celecoxib. For the first time, this indicates the requirement of investigating the removal of acetylenic group in this study showed that it might be a different binding site in COXs which may result in effective compounds.

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Development of 1h-Indazole Derivatives as Anti-Inflammatory Agents Using Computational Methods

NANAWARE,

CHABUKSWAR,

ADSULE

et al. 2024

Int J App Pharm

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Objective: Due to the rising prevalence of disorders linked to inflammation, there is a greater emphasis on the discovery and development of anti-inflammatory drugs, with a focus on producing new structural compounds. Methods: In this research, molecular docking and Molecular Dynamics (MD) simulation study were carried out to evaluate the 1H-indazole analogs as potent anti-inflammatory agents. Results: The compounds containing difluorophenyl, para-toulene and 4-methoxyphenyl group shows significant binding results (9.11, 8.80 and 8.46 kcal/mol respectively) when docked with Cyclooxygenase-2 (COX-2) enzyme 3NT1. The results of the MD simulation indicated that test compound BDF was relatively stable in the COX-2 enzymes active sites. The compound BDF-3NT1 demonstrated substantial affinities for binding with all of its aimed targets following a dynamic Molecular Mechanics with Generalized Born Surface Area (MM-GBSA) analysis. Conclusion: In accordance to this study, newly developed 1H-indazole compounds have the potential for treating inflammation.

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Design, Synthesis and Biological Screening of Aminoacetylenic Tetrahydrophthalimide Analogues as Novel Cyclooxygenase (Cox) Inhibitors

Cited by 3 publications

References 16 publications

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

Development of 1h-Indazole Derivatives as Anti-Inflammatory Agents Using Computational Methods

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