Publications
Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies
Discerning of isatin-based monoamine oxidase (MAO) inhibitors for neurodegenerative disorders by exploiting 2D, 3D-QSAR modelling and molecular dynamics simulation
Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies Mohamed E. Shaker,Hesham A. M. Goma,Izzeddin Alsalahat,Nadia A. A. Elkanzi,Amany A. Azouz,Mohamed Sadek Abdel-Bakky, show all Pages 1804-1817 | Received 10 May 2023, Accepted 27 Nov 2023, Published online: 28 Dec 2023 Cite this article https://doi.org/10.1080/07391102.2023.2293257 CrossMark LogoCrossMark Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days Full Article Figures & data References Supplemental Citations Metrics Reprints & Permissions Read this article Abstract NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes. Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs. Novel pyridopyrimidines, 9a-j, were prepared and their chemical structures were confirmed by NMR, mass and IR Spectra, and elemental analysis. The effect of the 9a-j compounds on COX-1 and COX-2 was assessed and it was found that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) was the most potent COX-2 inhibitor (IC50 = 0.54 uM) compared to celecoxib (IC50 = 1.11 uM) with selectivity indices of 6.56 and 5.12, respectively. The in vivo inhibition of paw edema of novel compounds 9a-j was measured using carrageenan-induced paw edema method, and that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) showed the best inhibitory activity in comparison with the other compounds and celecoxib. The gastroprotective effect of the potent derivatives 9d, 9e, 9f, 9 g and 9h was investigated. 2-Hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) and 7-(chlorophenyl)-hydrazino-5-(4-methoxyphenyl)-3H-pyrido[2,3-d)pyrimidin-4-one (9e) showed ulcer indices comparable to celecoxib (1 and 0.5 vs 0.5, respectively). Docking studies were carried out and they confirmed the mechanistic action of the designed compounds Keywords: COXs inhibitorsanti-inflammatorycelecoxibNSAIDspyridopyrimidines Disclosure statement No potential conflict of interest was reported by the author(s). Additional information Funding This research was funded by the Deanship of Scientific Research at Jouf University, Saudi Arabia through a research grant group to ME Shaker (DSR-2022-RG-0149). Share Related research People also read Recommended articles Cited by 5 Information for Authors R&D professionals Editors Librarians Societies Open access Overview Open journals Open Select Dove Medical Press F1000Research Opportunities Reprints and e-prints Advertising solutions Accelerated publication Corporate access solutions Help and information Help and contact Newsroom All journals Books Keep up to date Register to receive personalised research and resources by email Sign me up Taylor and Francis Group Facebook pageTaylor and Francis Group X Twitter pageTaylor and Francis Group Linkedin page Taylor and Francis Group Youtube pageTaylor and Francis Group Weibo page Copyright © 2025Informa UK Limited Privacy policy Cookies Terms & conditions Accessibility Registered in England & Wales No. 01072954 5 Howick Place | London | SW1P 1WG Taylor and Francis Group PDF Help
Development of Isopropyl-Tailed Chalcones as a New Class of Selective MAO-B Inhibitors for the Treatment of Parkinson’s Disorder
Design, Synthesis, Molecular Modeling, and Anticancer Evaluation of New VEGFR-2 Inhibitors Based on the Indolin-2-One Scaffold
Development and assessment of phospholipid-based luteolin-loaded lipid nanocapsules for skin delivery
Development of Halogenated-Chalcones Bearing with Dimethoxy Phenyl Head as Monoamine Oxidase-B Inhibitors
Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors
Development of bromo- and fluoro-based α, β-unsaturated ketones as highly potent MAO-B inhibitors for the treatment of Parkinson’s disease
Design, Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect
Design, synthesis, and biological evaluation of novel pyrido-dipyrimidines as dual topoisomerase II/FLT3 inhibitors in leukemia cells
Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-Diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists
Docking Study, Synthesis, and Anti-Inflammatory Potential of Some New Pyridopyrimidine-Derived Compounds
Development and Greenness Assessment of HPLC Method for Studying the Pharmacokinetics of Co-Administered Metformin and Papaya Extract
Design, Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect
Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach
Development of 3-methyl/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells