Zagazig University Digital Repository
Home
Thesis & Publications
All Contents
Publications
Thesis
Graduation Projects
Research Area
Research Area Reports
Search by Research Area
Universities Thesis
ACADEMIC Links
ACADEMIC RESEARCH
Zagazig University Authors
Africa Research Statistics
Google Scholar
Research Gate
Researcher ID
CrossRef
Design and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages
Faculty
Pharmacy
Year:
2022
Type of Publication:
ZU Hosted
Pages:
1-14
Authors:
Nermeen Awny Ahmed Mohamd
Staff Zu Site
Abstract In Staff Site
Journal:
Bioorganic Chemistry Elsevier Inc.
Volume:
124
Keywords :
Design , Synthesis , Novel 1,3,4-Oxadiazole , 1,2,4-Triazole Derivatives , Cyclooxygenase-2
Abstract:
In an attempt to obtain new candidates with potential anti-inflammatory activity, two series of 1,3,4-oxadiazole based derivatives (8a–g) and 1,2,4-triazole based derivatives (10a,b and 11a–g) were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. In vitro assays showed potent COX-2 inhibitory activity and selectivity of the novel designed compounds (IC50 = 0.04 – 0.16 μM, SI = 60.71 – 337.5) compared to celecoxib (IC50 = 0.045 μM, SI = 326.67). The anti-inflammatory and antioxidant activity of the synthesized compounds was investigated via testing their ability to inhibit pro-inflammatory [tumour necrosis factor (TNF-α) and interleukin- 6 (IL-6)] and oxidative stress [nitric oxide (NO) and reactive oxygen species (ROS)] markers production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Most of the novel compounds exhibited potent anti-inflammatory and antioxidant activity. In particular, the novel compounds showed excellent IL-6 inhibitory activity (IC50 = 0.96 – 11.14 μM) when compared to celecoxib (IC50 = 13.04 μM) and diclofenac sodium (IC50 = 22.97 μM). Moreover, the most potent and selective COX-2 inhibitor 11c (IC50 = 0.04 μM, SI = 337.5) displayed significantly higher activity against NO and ROS production compared to celecoxib (IC50 = 2.60 and 3.01 μM vs. 16.47 and 14.30 μM, respectively). Molecular modelling studies of the novel designed molecules into COX-2 active sites analysed their binding affinity. In-silico simulation studies indicated their acceptable physicochemical properties and pharmacokinetic profiles. This study suggests that the novel synthesized COX-2 inhibitors exert potent anti-inflammatory and antioxidant activity, highlighting their potential as promising therapeutic agents for the treatment of inflammation and oxidative stress-related diseases.
Author Related Publications
Nermeen Awny Ahmed Mohamd, "Synthesis of some new Pyrazole Derivatives of Possible Biological Interest", لايوجد, 1900
More
Nermeen Awny Ahmed Mohamd, "Synthesis and Anti-inflammatory activity of Novel Pyrimidine derivatives ", لايوجد, 1900
More
Nermeen Awny Ahmed Mohamd, "Synthesis and Anti-inflammatory activity of Novel Pyrazole derivatives", لايوجد, 1900
More
Nermeen Awny Ahmed Mohamd, "Utility of 2-Hydrazino-4,6-Dimethyl –Pyrimidine in Heterocyclic Synthesis ", لايوجد, 1900
More
Nermeen Awny Ahmed Mohamd, "Design, synthesis and in-vitro antitumor activity of novel phthalazin-1,4-dione/chalcone hybrids and phthalazin-1,4-dione/pyrazoline hybrids", JCPRC5, 2015
More
Department Related Publications
Amany Mohamed Mohamed Elmahmoudy Sanger, "Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors", mdpi, 2022
More
Tarek Mohamed Salah Rashad, "Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors", mdpi, 2022
More
Amany Mohamed Mohamed Elmahmoudy Sanger, "Synthesis, Antibacterial Evaluation, and Computational Studies of a Diverse Set of Linezolid Conjugates", mdpi, 2022
More
Tarek Mohamed Salah Rashad, "New Multi-Targeted Antiproliferative Agents: Design and Synthesis of IC261-Based Oxindoles as Potential Tubulin, CK1 and EGFR Inhibitors", mdpi, 2021
More
Tarek Mohamed Salah Rashad, "Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction", Taylor & Francis Group, 2021
More
جامعة المنصورة
جامعة الاسكندرية
جامعة القاهرة
جامعة سوهاج
جامعة الفيوم
جامعة بنها
جامعة دمياط
جامعة بورسعيد
جامعة حلوان
جامعة السويس
شراقوة
جامعة المنيا
جامعة دمنهور
جامعة المنوفية
جامعة أسوان
جامعة جنوب الوادى
جامعة قناة السويس
جامعة عين شمس
جامعة أسيوط
جامعة كفر الشيخ
جامعة السادات
جامعة طنطا
جامعة بنى سويف