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Design, synthesis, and antihypertensive activity of new pyrimidine derivatives endowing new pharmacophores

  • Ahmed M. Farghaly
  • Omaima M. AboulWafaEmail author
  • Yaseen A. M. Elshaier
  • Waleed A. Badawi
  • Haridy H. Haridy
  • Heba A. E. Mubarak
Original Research
  • 63 Downloads

Abstract

A new series of achiral pyrimidine derivatives based on nifedipine-like structure was designed and synthesized. These pyrimidyl derivatives contained hydrazine, hydrazones, acetohydrazide, differently substituted benzylidene functionalities, benzosulfohydrazine, various heterocycles such as pyrazole, pyrazolidinedione, thiazoline, and thiazolidinone rings, and fused ring systems such as triazolopyrimidine and pyrimidotriazine rings. Compounds 5a, 5b, 11b, 8b, 9b–d, and 15b showed a decrease in mean arterial rabbit blood pressure (MABP) ranging from 51.4 to 78.2 mmHg in rabbits in comparison with nifedipine-treated rabbits. Among these derivatives, compounds 5a, 5b, 9b, and 9c were found to exhibit calcium channel blockade activity on preparations of rabbit aortae. They exhibited relaxation in the range of 89.2% to 74.4% in comparison to nifedipine (57.6%) as well as a decrease in heart rate. Histopathological effect of compounds 5a,b on the expression of endothelial nitric oxide synthase (eNOS) was also examined on rat aorta. An intense expression of eNOS immune staining in aortic endothelium was seen for compound 5b indicating that it lowered blood pressure via activation of eNOS expression in aorta.

Keywords

Nifedipine Pyrimidines ENOS Antihypertensive Histopathology SAR 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed involving animals were in accordance with the ethical standards. The experimental protocol was approved by Animal Care and Use Committee, Faculty of Pharmacy, Alexandria University (ACUC Project Number 16/1).

Supplementary material

44_2019_2289_MOESM1_ESM.docx (7.3 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ahmed M. Farghaly
    • 1
  • Omaima M. AboulWafa
    • 1
    Email author
  • Yaseen A. M. Elshaier
    • 2
  • Waleed A. Badawi
    • 3
  • Haridy H. Haridy
    • 4
  • Heba A. E. Mubarak
    • 5
  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Organic and Medicinal Chemistry, Faculty of PharmacyUniversity of Sadat CityMonofiaEgypt
  3. 3.Department of Pharmaceutical Chemistry, Faculty of PharmacyDamanhour UniversityDamanhourEgypt
  4. 4.Department of Pharmacology, Faculty of MedicineAl-Azhar University (Assiut Branch)AssiutEgypt
  5. 5.Department of Histology and Cell Biology, Faculty of MedicineAssiut UniversityAssiutEgypt

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