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Newly synthesized piperazine derivatives as tyrosinase inhibitors: in vitro and in silico studies

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Abstract

In this study, a series of new organic compounds with piperazine as a fundamental skeleton was synthesized and evaluated for their tyrosinase inhibitory potentials by in vitro and in silico studies. The in vitro studies have shown that compounds 10a and 10b bearing 1,2,4, triazole nucleus could be considered potent tyrosinase inhibitors with IC50 values of 31.2 ± 0.7 and 30.7 ± 0.2 µM, respectively. 10b (Ki = 9.54 µM, mixed type inhibition) with the lowest IC50 value among derivatives was selected to determine kinetic constants and inhibition types. Furthermore, molecular docking analysis was performed for all compounds and it was observed that 4b, 5a, 4c, and 10b showed promising inhibitory effect on tyrosinase activity. Based on docking results, ADME predictions and in vitro studies, 10b might be considered suitable oral drug candidates for further studies.

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References

  1. C.S. Nunes, K. Vogel, in Enzymes, in Human and Animal Nutrition. ed. by C.S. Nunes, V. Kumar (Elsevier, Academic Press, 2018), pp. 403–412

    Google Scholar 

  2. Á. Sánchez-Ferrer, J. Neptuno Rodríguez-López, F. García-Cánovas, F. García-Carmona, Biochim. Biophys. Acta, 1247(1), 1–11 (1995). https://doi.org/10.1016/0167-4838(94)00204-T

  3. G. Prota, Med. Res. Rev. 8(4), 525–556 (1988). https://doi.org/10.1002/med.2610080405

    Article  CAS  PubMed  Google Scholar 

  4. H. Ando, H. Kondoh, M. Ichihashi, V.J. Hearing, J. Invest. Dermatol. 127(4), 751–761 (2007). https://doi.org/10.1038/sj.jid.5700683

    Article  CAS  PubMed  Google Scholar 

  5. L.L. Baxter, W.J. Pavan, Wiley Interdiscip. Rev. Dev. Biol. 2(3), 379–392 (2013). https://doi.org/10.1002/wdev.72

    Article  CAS  Google Scholar 

  6. T. Hasegawa, Int. J. Mol. Sci. 11(3), 1082–1089 (2010). https://doi.org/10.3390/ijms11031082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. T. Pillaiyar, M. Manickam, V. Namasivayam, J. Enzyme Inhib. Med. Chem. 32(1), 403–425 (2017). https://doi.org/10.1080/14756366.2016.1256882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. S. Briganti, E. Camera, M. Picardo, Pigment Cell Res. 16(2), 101–110 (2003). https://doi.org/10.1034/j.1600-0749.2003.00029.x

    Article  PubMed  Google Scholar 

  9. L. Ni-Komatsu, C. Tong, G. Chen, N. Brindzei, S.J. Orlow, Mol. Pharmacol. 74(6), 1576–1586 (2008). https://doi.org/10.1124/mol.108.050633

    Article  CAS  PubMed  Google Scholar 

  10. R.F. Hurrell, P.-A. Finot, Adv. Exp. Med. Biol. 177, 423–435 (1984). https://doi.org/10.1007/978-1-4684-4790-3_20

    Article  CAS  PubMed  Google Scholar 

  11. M.R. Loizzo, R. Tundis, F. Menichini, Compr. Rev. Food Sci. F. 11(4), 378–398 (2012). https://doi.org/10.1111/j.1541-4337.2012.00191.x

    Article  CAS  Google Scholar 

  12. S. Parvez, M. Kang, H.-S. Chung, H. Bae, Phytother. Res. 21(9), 805–816 (2007). https://doi.org/10.1002/ptr.2184

    Article  CAS  PubMed  Google Scholar 

  13. T. Damghani, S. Hadaegh, M. Khoshneviszadeh, S. Pirhadi, R. Sabet, M. Khoshneviszadeh, N. Edraki, J. Mol. Struct. 1222, 128876–128876 (2020). https://doi.org/10.1016/j.molstruc.2020.128876

    Article  CAS  Google Scholar 

  14. D. Yang, L. Wang, J. Zhai, N. Han, Z. Liu, S. Li, J. Yin, Food Chem. 336, 127714–127714 (2021). https://doi.org/10.1016/j.foodchem.2020.127714

    Article  CAS  PubMed  Google Scholar 

  15. H. Hosseinpoor, A. Iraji, N. Edraki, S. Pirhadi, M. Attarroshan, M. Khoshneviszadeh, M. Khoshneviszadeh, Chem. Biodivers. 17(8), e2000285 (2020). https://doi.org/10.1002/cbdv.202000285

    Article  CAS  PubMed  Google Scholar 

  16. H. Raza, M. A. Abbasi, R. Aziz ur, S. Z. Siddiqui, M. Hassan, Q. Abbas, H. Hong, S. A. A. Shah, M. Shahid, S. Y. Seo, Bioorg. Chem., 94, 103445–103445 (2020). https://doi.org/10.1016/j.bioorg.2019.103445

  17. S.H. Shelke, P.C. Mhaske, S.K. Kasam, V.D. Bobade, J. Heterocycl. Chem. 51(6), 1893–1897 (2014). https://doi.org/10.1002/jhet.1910

    Article  CAS  Google Scholar 

  18. Z. Shi, Z. Zhao, M. Huang, X. Fu, C. R. Chim. 18(12), 1320–1327 (2015). https://doi.org/10.1016/j.crci.2015.09.005

    Article  CAS  Google Scholar 

  19. S.H. Shelke, P.C. Mhaske, S. Narkhade, V.D. Bobade, J. Heterocycl. Chem. 51(4), 1151–1156 (2014). https://doi.org/10.1002/jhet.1789

    Article  CAS  Google Scholar 

  20. R. Listro, S. Stotani, G. Rossino, M. Rui, A. Malacrida, G. Cavaletti, M. Cortesi, C. Arienti, A. Tesei, D. Rossi, M.D. Giacomo, M. Miloso, S. Collina, Front. Chem. 8, 495–495 (2020). https://doi.org/10.3389/fchem.2020.00495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. G.D. Hatnapure, A.P. Keche, A.H. Rodge, S.S. Birajdar, R.H. Tale, V.M. Kamble, Bioorg. Med. Chem. Lett. 22(20), 6385–6390 (2012). https://doi.org/10.1016/j.bmcl.2012.08.071

    Article  CAS  PubMed  Google Scholar 

  22. B. Selvakumar, N. Gujjar, M. Subbiah, K.P. Elango, Med. Chem. Res. 27(2), 512–519 (2018). https://doi.org/10.1007/s00044-017-2077-5

    Article  CAS  Google Scholar 

  23. J.A. Wiles, B.J. Bradbury, M.J. Pucci, Expert Opin. Ther. Pat. 20(10), 1295–1319 (2010). https://doi.org/10.1517/13543776.2010.505922

    Article  CAS  PubMed  Google Scholar 

  24. M. Baumann, I.R. Baxendale, Beilstein J. Org. Chem. 9(1), 2265–2319 (2013). https://doi.org/10.3762/bjoc.9.265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. S.J.Y. Macalino, V. Gosu, S. Hong, S. Choi, Arch. Pharm. Res. 38(9), 1686–1701 (2015). https://doi.org/10.1007/s12272-015-0640-5

    Article  CAS  PubMed  Google Scholar 

  26. X. Meng, H.-X. Zhang, M. Mezei, M. Cui, Curr. Comput. Aided-Drug 7(2), 146–157 (2011). https://doi.org/10.2174/157340911795677602

    Article  CAS  Google Scholar 

  27. S. Başoğlu Özdemir, J. Turkish Chem. Soc., 3(3), 515–534 (2016). https://doi.org/10.18596/jotcsa.55734

  28. M.Y. Mentese, H. Bayrak, Y. Uygun, A. Mermer, S. Ulker, S.A. Karaoglu, N. Demirbas, Eur. J. Med. Chem. 67, 230–242 (2013). https://doi.org/10.1016/j.ejmech.2013.06.045

    Article  CAS  PubMed  Google Scholar 

  29. E. Rajanarendar, K. Thirupathaiah, S. Ramakrishna, D. Nagaraju, Chin. Chem. Lett. 26(12), 1511–1513 (2015). https://doi.org/10.1016/j.cclet.2015.07.024

    Article  CAS  Google Scholar 

  30. A. Balabani, D.J. Hadjipavlou-Litina, K.E. Litinas, M. Mainou, C.-C. Tsironi, A. Vronteli, Eur. J. Med. Chem. 46(12), 5894–5901 (2011). https://doi.org/10.1016/j.ejmech.2011.09.053

    Article  CAS  PubMed  Google Scholar 

  31. H. Bayrak, A. Demirbas, N. Demirbas, S.A. Karaoglu, Eur. J. Med. Chem. 44(11), 4362–4366 (2009). https://doi.org/10.1016/j.ejmech.2009.05.022

    Article  CAS  PubMed  Google Scholar 

  32. Z. Peng, G. Wang, Q.-H. Zeng, Y. Li, Y. Wu, H. Liu, J.J. Wang, Y. Zhao, Food Chem. 341, 128265–128265 (2021). https://doi.org/10.1016/j.foodchem.2020.128265

    Article  CAS  PubMed  Google Scholar 

  33. B.D. Vanjare, P.G. Mahajan, N.C. Dige, H. Raza, M. Hassan, Y. Han, S.J. Kim, S.-Y. Seo, K.H. Lee, Mol. Divers. (2020). https://doi.org/10.1007/s11030-020-10102-5

    Article  PubMed  Google Scholar 

  34. U. Cakmak, F. Oz-Tuncay, S. Basoglu-Ozdemir, E. Ayazoglu-Demir, İ Demir, A. Colak, S. Celik-Uzuner, S.S. Erdem, N. Yildirim, Med. Chem. Res. 30(10), 1886–1904 (2021). https://doi.org/10.1007/s00044-021-02785-8

    Article  CAS  Google Scholar 

  35. C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Adv. Drug Del. Rev. 23(1–3), 3–25 (1997). https://doi.org/10.1016/S0169-409X(96)00423-1

    Article  CAS  Google Scholar 

  36. D.F. Veber, S.R. Johnson, H.-Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, J. Med. Chem. 45(12), 2615–2623 (2002). https://doi.org/10.1021/jm020017n

    Article  CAS  PubMed  Google Scholar 

  37. W. T. Ismaya, H. t. J. Rozeboom, A. Weijn, J. J. Mes, F. Fusetti, H. J. Wichers, B. W. Dijkstra, Biochemistry, 50(24), 5477–5486 (2011). https://doi.org/10.1021/bi200395t

  38. S. Jolivet, N. Arpin, H.J. Wichers, G. Pellon, Mycol. Res. 102(12), 1459–1483 (1998). https://doi.org/10.1017/S0953756298006248

    Article  CAS  Google Scholar 

  39. L. Gou, Z.-R. Lü, D. Park, S.H. Oh, L. Shi, S.J. Park, J. Bhak, Y.-D. Park, Z.-L. Ren, F. Zou, J. Biomol. Struct. Dyn. 26(3), 395–401 (2008). https://doi.org/10.1080/07391102.2008.10507254

    Article  CAS  Google Scholar 

  40. J.C. Espin, M. Morales, R. Varon, J. Tudela, F. Garciacanovas, Anal. Biochem. 231(1), 237–246 (1995). https://doi.org/10.1006/abio.1995.1526

    Article  CAS  PubMed  Google Scholar 

  41. Y. Ozdemir, O. Bekircan, A. Colak, C. Dokuzparmak, Indian J. Chem., 59, 1409–1417 (2020). http://nopr.niscair.res.in/handle/123456789/55444

  42. Y. Kolcuoğlu, A. Colak, E. Sesli, M. Yildirim, N. Saglam, Food Chem. 101(2), 778–785 (2007). https://doi.org/10.1016/j.foodchem.2006.02.035

    Article  CAS  Google Scholar 

  43. C. Molinspiration (2016). http://www.molinspiration.com/cgi-bin/properties

  44. Y.H. Zhao, M.H. Abraham, J. Le, A. Hersey, C.N. Luscombe, G. Beck, B. Sherborne, I. Cooper, Pharm. Res. 19(10), 1446–1457 (2002). https://doi.org/10.1023/A:1020444330011

    Article  CAS  PubMed  Google Scholar 

  45. S. Wavefunction (2016). http://wavefun.com

  46. J.J.P. Stewart, J. Mol. Model. 15(7), 765–805 (2009). https://doi.org/10.1007/s00894-008-0420-y

    Article  CAS  PubMed  Google Scholar 

  47. Y. Zhao, D.G. Truhlar, Acc. Chem. Res. 41(2), 157–167 (2008). https://doi.org/10.1021/ar700111a

    Article  CAS  PubMed  Google Scholar 

  48. Y. Zhao, D.G. Truhlar, Theor. Chem. Acc. 120(1–3), 215–241 (2008). https://doi.org/10.1007/s00214-007-0310-x

    Article  CAS  Google Scholar 

  49. O. Trott, A.J. Olson, J. Comput. Chem. 31(2), 455–461 (2009). https://doi.org/10.1002/jcc.21334

    Article  CAS  Google Scholar 

  50. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, J. Comput. Chem. 30(16), 2785–2791 (2009). https://doi.org/10.1002/jcc.21256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Accelrys Software Inc. Release 4.0, San Diego, Discovery Studio Modeling Environment (2013).

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Acknowledgements

This work was supported by the Scientific and Research Council of Turkey (TUBITAK) [No. 117Z199].

Funding

This work was supported by the Scientific and Research Council of Turkey (TUBITAK) [No. 117Z199], which is hereby gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Karadeniz Technical University, 61080, Trabzon, Turkey

    Cigdem Dokuzparmak, Fulya Oz Tuncay, Serap Basoglu Ozdemir, Busra Kurnaz, Ahmet Colak & Nuri Yildirim

  2. Department of Chemistry Faculty of Arts and Sciences, Marmara University, 34722, İstanbul, Turkey

    Ilke Demir & Safiye Sag Erdem

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  1. Cigdem Dokuzparmak
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  2. Fulya Oz Tuncay
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  3. Serap Basoglu Ozdemir
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Correspondence to Ahmet Colak.

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Dokuzparmak, C., Oz Tuncay, F., Basoglu Ozdemir, S. et al. Newly synthesized piperazine derivatives as tyrosinase inhibitors: in vitro and in silico studies. J IRAN CHEM SOC 19, 2739–2748 (2022). https://doi.org/10.1007/s13738-021-02487-3

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