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Dipyrimido[4,5-b:5,4-e][1,4]thiazine: synthesis and their enzyme inhibitory activity assessment on soybean 15-lipoxygenase

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Abstract

A series of new derivatives of dipyrimido[4,5-b:5,4-e][1,4] thiazine were synthesized by treatment of 5-amino-6-methyl-2-morpholino-4-pyrimidinethiol (1) with 5-bromo-2,4-dichloro-6-methylpyrimidine (2) in the presence of triethylamine and ethanol and subsequently with various secondary amines in EtOH/DMF. The thioether derivative 3 and heterocyclization products 4a–f were characterized by elemental analysis and spectroscopic techniques. The 15-LO inhibitory activities of the new synthesized compounds were also evaluated. The results show that compound 4e has the best IC50 of 15-LO inhibition (IC50 = 14.4 µM) but when all the products were theoretically docked into 15-LO, the GOLD scores of compounds 4e and 4d are 43.67 and 43.39 respectively, which show the best results. We suggest that the hydrogen bond interaction between Ser489 of 15-LO and the nitrogen of piperazine ring of compound 4e appears to play major role in lipoxygenase inhibition.

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Acknowledgments

The authors gratefully acknowledge Ferdowsi University of Mashhad for partial support of this project (P 25422/3).

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, 91775-1436, Mashhad, Iran

    Azam Karimian, Hossein Eshghi, Mehdi Bakavoli, Ali Shiri, Mohammad Saadatmandzadeh, Tayebe Asghari & Hasanali Moradi

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  1. Azam Karimian
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  2. Hossein Eshghi
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Correspondence to Hossein Eshghi.

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Karimian, A., Eshghi, H., Bakavoli, M. et al. Dipyrimido[4,5-b:5,4-e][1,4]thiazine: synthesis and their enzyme inhibitory activity assessment on soybean 15-lipoxygenase. J IRAN CHEM SOC 12, 1501–1508 (2015). https://doi.org/10.1007/s13738-015-0620-1

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