Open AccessSynthesis, Molecular Modelling and Biological Evaluation of Novel Pyrimidine Derivatives as Anti-inflammatory Agents
Author(s) -
Nadia Ahmed,
Shahira Nofal,
Samir M. Awad
Publication year - 2020
Publication title -
journal of pharmaceutical research international
Language(s) - English
Resource type - Journals
ISSN - 2456-9119
DOI - 10.9734/jpri/2020/v32i2230771
Subject(s) - ibuprofen , pyrimidine , chemistry , pharmacology , docking (animal) , potency , in vitro , carrageenan , combinatorial chemistry , stereochemistry , medicine , biochemistry , veterinary medicine
Aim: As part of ongoing studies in developing new anti-inflammatory agents, 2-thioxo-1,2,3,4-tetrahydropyrimidine derivative 1 was synthesized by direct Biginelli condensation and used for the synthesis of novel series of pyrimidin-2-thione derivatives (2a-d to 7a-b).
Materials and Methods: All compounds were examined for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay in comparison to ibuprofen, as a reference drug. Molecular docking studies were carried out using SYBLYL-X v.2.1 software.
Study Design: A series of pyrimidine derivatives were synthesized by a simple and available method leads to a molecule of promising anti-inflammatory activity, the docking studies show good agreement with anti-inflammatory results. Future researches are recommended to assure the importance of these new derivatives for various applications.
Place and Duration of Study: Pharmaceutical Organic Chemistry Department and Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt, between February 2018 and March 2019.
Results: Compounds showed 61 to 86% anti-inflammatory activity where-as ibuprofen showed 69% activity. Compounds 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 7a, 7b induced strong anti-inflammatory activity, comparable with that of ibuprofen, they showed significantly difference at 4h post-carrageenan. Compound 3c (86%) showed the best result of edema inhibition in rats. Moreover, compounds 1, 2c and 3c were subjected to in vitro enzyme assay investigations against COX-1 and COX-2. All tested compounds showed higher potency towards COX-2 over COX-1. Compound 3c realized higher potency towards COX-2 (IC50= 0.046 μM) than compounds 1(IC50= 0.21 μM) and 2c (IC50=0.11 μM) as well as ibuprofen (IC50= 43.628 μM). Structure-activity relationship (SAR) has been discussed.
Conclusion: A series of pyrimidine derivatives were synthesized by a simple and available method gave a molecule of promising anti-inflammatory activity, the docking studies showed good agreement with anti-inflammatory results.