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

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.
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Copyright (c) 2020 Kezhal M. Salih, Dana Ameen, Aras Najmaddin Hamad, Aryan Rizgar Ganjo, Sarbast Muhammed (Author)

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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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References

  1. Mistry K, Desai K. Synthesis of novel heterocyclic 4-thiazolidinone derivatives and their antibacterial activity. J Chem 2004; 1(4):189–93.
  2. Manojkumar P, Ravi T, Subbuchettiar G. Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells. Acta Pharma 2009; 59(2):159–70.
  3. Palekar VS, Damle AJ, Shukla SR. Synthesis and antibacterial activity of some novel bis-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and bis-4-thiazolidinone derivatives from terephthalic dihydrazide. Eur J Med Chem 2009; 44(12):5112–6.
  4. Arora P, Arora V, Lamba H, Wadhwa D. Importance of heterocyclic chemistry: A review. Int J Pharm Sci Res 2012; 3(9):2947.
  5. Bassyouni FA, Abu-Bakr SM, Hegab KH, El-Eraky W, Ahmed A, Rehim MEA. Synthesis of new transition metal complexes of 1H-perimidine derivatives having antimicrobial and anti-inflammatory activities. Res Chem Intermed 2012; 38(7):1527–50.
  6. Malladi S, Isloor AM, Isloor S, Akhila DS, Fun H-K. Synthesis, characterization and antibacterial activity of some new pyrazole based Schiff bases. Arab J of Chem 2013; 6(3):335–40.
  7. Liu KC, Chen HH. Reaction of 2‐hydrazinoperimidine with acetylacetone. J Heterocycl Chem 1984; 21(3):911–2.
  8. Isikdag I, Incesu Z, Gülnaz D, Özkay Y. Cytotoxic Effects of Some Perimidine Derivatives on F2408 and 5Rp7 Cell Lines/Perimidin Türevlerinin F2408 ve 5Rp7 Hücre Hatlari Üzerine Sitotoksik Etkileri. FABAD J Pharm Sci 2008; 33(3):135.
  9. Herbert JM, Woodgate PD, Denny WA. Potential antitumor agents. 53. Synthesis, DNA binding properties, and biological activity of perimidines designed as minimal DNA-intercalating agents. J Med Chem 1987; 30(11):2081–6.
  10. Pozharskii AF, Dal'Nikovskaya V. Perimidines. Russ Chem Rev 1981; 50(9):816–35.
  11. Davis R, Tamaoki N. Novel photochromic spiroheterocyclic molecules via oxidation of 1, 8-diaminonaphthalene. Organic lett 2005; 7(8):1461–4.
  12. Kahveci B, Karaali N. Synthesis of new perimidine derivatives from the reaction of 1, 8-diaminonapthalene with iminoester hydrochlorides. J Chem Res 2013; 37(6).
  13. Nikolaidis I, Favini-Stabile S, Dessen A. Resistance to antibiotics targeted to the bacterial cell wall. Protein Sci 2014; 23(3):243–59.
  14. Helander I, Nurmiaho-Lassila E-L, Ahvenainen R, Rhoades J, Roller S. Chitosan disrupts the barrier properties of the outer membrane of Gram-negative bacteria. Int J Food Microbiol 2001; 71(2-3):235–44.
  15. Varsha G, Arun V, Robinson P, Sebastian M, Varghese D, Leeju P, et al. Two new fluorescent heterocyclic perimidines: first syntheses, crystal structure, and spectral characterization. Tetrahedron Lett 2010; 51(16):2174–7.
  16. Salih KM, Azeez HJ. Synthesis, characterization and biological activity of 2-Aryl-2, 3-dihydro-1H-perimidine. Res Pharm Biotech 2014; 5(1):1–6.
  17. Nile SH, Ko EY, Kim DH, Keum Y-S. Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity. Rev Bras Farmacogn 2016; 26(1):50–5.
  18. Dannhardt G, Kiefer W. Cyclooxygenase inhibitors–current status and future prospects. Eur J Med Chem 2001; 36(2):109–26.
  19. Kalgutkar AS, Crews BC, Saleh S, Prudhomme D, Marnett LJ. Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors. Bioorg Med Chem 2005; 13(24):6810–22.
  20. Flower RJ. The development of COX2 inhibitors. Nat Rev Drug Disc 2003; 2(3):179.
  21. Hadjipavlou-Litina D. Quantitative structure-activity relationship (QSAR) studies on non steroidal anti-inflammatory drugs (NSAIDs). Curr Med Chem 2000; 7(4):375–88.
  22. Abdou WM, Ganoub NA, Sabry E. Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo [1, 5-b] pyridazines as antinociceptive/ anti-inflammatory agents. Beilstein J Org Chem 2013; 9:1730.
  23. Zhang HJ, Wang XZ, Cao Q, Gong GH, Quan ZS. Design, synthesis, anti-inflammatory activity, and molecular docking studies of perimidine derivatives containing triazole. Bioorg Med Chem Lett 2017; 27(18):4409–14.
How to Cite
Salih, K. M., Ameen, D., Hamad, A. N., Ganjo, A. R., & Muhammed, S. (2020). Synthesis and pharmacological profile of some new 2-substituted-2, 3-dihydro-1H-perimidine. Zanco Journal of Medical Sciences (Zanco J Med Sci), 24(1), 68–79. https://doi.org/10.15218/zjms.2020.010

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