Abstract
Pain is one of many medical problems of modern society. Together with a number of other diseases such as heart attacks, strokes, tumors, etc. it ranks among the first in manifestation. There are a huge number of medical drugs more or less effective against pain in a practice. Globally, the searching of new molecules with analgesic activity and better selectivity or greater effect at lower doses continues. In addition, some groups trying to improve the properties of known molecules in medical practice as various heterocyclic compounds by modifying one or another of their part. Other groups work on the creation of new mimetics of natural molecules with well established physiological activity. In this global context, here we report the synthesis of two new compounds which are hybrid molecules between the specifically substituted pyrrole (Pyr) and analogues of Tyr-MIF-1 peptide. All investigations on the analgesic activity show better activity at the same dose than natural Tyr-MIF-1 peptide for the analogue Pyr-Tyr-Phe-Leu-Ala-OH. Compound Pyr-Ala-Leu-Phe-Tyr-OH has no better effect comparable to that of the parent peptide. The obtained results clearly show that it is essential that Tyr residue occupies N-terminal position of MIF-1 analogue. The lack of better activity of the analogue Pyr-Ala-Leu-Phe-Tyr-OH reveals that Pyr residue does not influence on the analgesic activity. In addition we found that C-terminal amide function generally presented in natural MIF-1 is not absolutely necessary for activity.
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Acknowledgments
Borislav P. Borisov has received some financial support for its Ph.D. thesis development by the Grant No. BG051PO001-3.3.06-0059, financed by the European Social Fund and Operational Programme Human Resources Development (2007–2013) and co-financed by Bulgarian Ministry of Education and Science. Dancho L. Danalev has received some financial support for chemical synthesis of aim compounds by the Grant 11385 with Scientific Fund of University of Chemical Technology and Metallurgy of Sofia, Bulgaria. Adriana I. Bocheva and Hristina H. Nocheva have received some financial support for analgesic activity determination by the Grant 42/2014 with Medical University of Sofia.
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Stanislava P. Vladimirova, Dessislava A. Marinkova, Emilia D. Naydenova and Valentin S. Lozanov declare that they have no conflict of interest.
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Hristina H. Nocheva and Adriana I. Bocheva declare that all the experiments with animals described in this article were conducted between 9.00 and 12.00 a.m., and according to the ‘‘Principles of laboratory animal care’’ 9 (NIH publication No. 85-23, revised 1985), and the rules of the the Animal Care and Use Committee of the Medical University of Sofia.
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Danalev, D.L., Vladimirova, S.P., Borisov, B.P. et al. Synthesis and Analgesic Activity of New Analogues of Tyr-MIF Including Pyrrole Moiety. Int J Pept Res Ther 22, 243–248 (2016). https://doi.org/10.1007/s10989-015-9502-8
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DOI: https://doi.org/10.1007/s10989-015-9502-8