Synthesis and pharmacological profile of some new 2-substituted-2, 3-dihydro-1H-perimidine

Kezhal M. Salih; Dana Ameen; Aras Najmaddin Hamad; Aryan Rizgar Ganjo; Sarbast Muhammed

doi:10.15218/zjms.2020.010

Authors

Kezhal M. Salih Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Dana Ameen Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Aras Najmaddin Hamad Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Aryan Rizgar Ganjo Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Sarbast Muhammed Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

DOI:

https://doi.org/10.15218/zjms.2020.010

Keywords:

1,8-diaminonaphthalene, Carbonyl compounds, v, 2,3-dihyroperimidin, Antibacterial

Abstract

Background and objective: The development of new antimicrobial drugs is still demanded as there is increasing resistance of microorganisms to currently available antimicrobial drugs and searches for safer nonsteroidal anti-inflammatory agents with greater cyclooxygenase COX II selectivity is challenging. The new series of 2-substituted-2,3-dihydro-1H-perimidine (4a-j) that are close analogs to Naproxen 5, might inhibit COX II enzyme in a similar manner to naproxen 5. This study aimed to synthesize some new heterocyclic compounds for enhancing biological activity.

Methods: 1,8-Diaminonaphthalene 2 was condensed with a variety of aldehydes and ketones 3 to afford a new series of 2-substituted-2,3-dihydro-1H-perimidines4a-j using a suitable synthetic strategy. All the synthesized 2,3-dihydro-1H-perimidine compounds 4a-jwere screened for their invitro antimicrobial activities against two identifiable strains using the agar diffusion method. At the same time, the synthesized pyrimidine derivatives 4a-were evaluated for their COX inhibition activity. Supplementary to these, the constitutions of the newly synthesized 2,3-dihydro-1H-perimidines 4a-j had been confirmed on the basis of their IR, ¹H- and ¹³C-NMR spectral data.

Results: The synthesized 2-substituted-2,3-dihydro-1H-perimidine compounds 4a-j exhibited promising antibacterial activity against Escherichia coli microorganism, while none of the synthesized derivatives 4a-jshowed likely result against Staphylococcus aureus strain. In addition, compound 4b had the most potent anti-inflammatory activity with an inhibition rate of 47% at 1000 nM.

Conclusion: The synthesized products4a-j possessed antibacterial activity (towards Escherichia coli microorganism; however, compounds 4c,4e, and 4j took the highest activity) and anti-inflammatory activity (compound 4b showed the highest inhibition rate).

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