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Chalcones and their pyrazine analogs: synthesis, inhibition of aldose reductase, antioxidant activity, and molecular docking study

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Abstract

Chalcones and their pyrazine analogs synthesized by Claisen–Schmidt condensation were tested for inhibition of aldose reductase, which is the key enzyme in the development of secondary diabetic complications. The most active compounds exerted IC50 values within the micromolar scale, and their interactions with the enzyme were described in a molecular docking study. Antioxidant activity of several representative compounds was explored in DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, revealing significant scavenging for 4-hydroxy-substituted derivatives endowed with electron-donating methoxy substituent in position 3 of the ring B. To conclude, the novel chalcones hydroxylated and methoxylated in the B-ring and their pyrazine analogs exhibited significant aldose reductase inhibition activity, albeit lower in comparison with the reference epalrestat. Medium antioxidant activity (not exceeding the antioxidant efficacy of the standard Trolox) was shown by the representative compounds tested.

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References

  1. Dimmock JR, Elias DW, Beazely MA, Kandepu NM (1999) Curr Med Chem 6:11259

    Google Scholar 

  2. Bukhari SNA, Jasamai M, Jantan I, Ahmad W (2013) Mini-Rev Org Chem 10:73

    Article  CAS  Google Scholar 

  3. Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L (2015) Expert Opin Ther Patents 25:351

    Article  CAS  Google Scholar 

  4. Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z (2017) Chem Rev 117:7762

    Article  CAS  Google Scholar 

  5. Mahapatra DK, Bharti SK, Asati V (2015) Eur J Med Chem 101:496

    Article  CAS  Google Scholar 

  6. Jez JM, Flynn TG, Penning TM (1997) Biochem Pharmacol 54:639

    Article  CAS  Google Scholar 

  7. Ruiz FX, Moro A, Gallego O, Ardevol A, Rovira C, Petrash JM, Pares X, Farres J (2011) Chem Biol Interact 191:199

    Article  CAS  Google Scholar 

  8. Ni LM, Meng CQ, Sikorski JA (2004) Expert Opin Ther Patents 14:1669

    Article  CAS  Google Scholar 

  9. Grewal AS, Bhardwaj S, Pandita D, Lather V, Sekhon BS (2016) Mini Rev Med Chem 16:120

    Article  CAS  Google Scholar 

  10. Okuyama T, Okada Y, Shibata S, Nagata N, Iwata S (1999) Preparation of chalcone derivatives as aldose reductase inhibitors. Jpn Kokai Tokkyo Koho JP 11349521 A2

  11. Chlupacova M, Opletalova V (2004) Chem Listy 98:320

    CAS  Google Scholar 

  12. Mahapatra DK, Asati V, Bharti SK (2015) Eur J Med Chem 92:839

    Article  CAS  Google Scholar 

  13. Rahman MH, Jha MK, Suk K (2016) Curr Pharm Des 22:738

    Article  Google Scholar 

  14. Sahu NK, Balbhadra SS, Choudhary J, Kohli DV (2012) Curr Med Chem 19:209

    Article  CAS  Google Scholar 

  15. Shibata S (2000) Yakugaku Zasshi-J Pharm Soc Jpn 120:849

    Article  CAS  Google Scholar 

  16. Katritzky AR, Pozharski AF (2000) Handbook of heterocyclic chemistry. Elsevier, Oxford

    Google Scholar 

  17. Joule JA, Mill K (2010) Heterocyclic chemistry. Wiley and Blackwell, Oxford

    Google Scholar 

  18. Rojas J, Dominguez JN, Charris JE, Lobo G, Paya M, Ferrandiz ML (2002) Eur J Med Chem 37:699

    Article  CAS  Google Scholar 

  19. Li RS, Kenyon GL, Cohen FE, Chen XW, Gong BQ, Dominguez JN, Davidson E, Kurzban G, Miller RE, Nuzum EO, Rosenthal PJ, McKerrow JH (1995) J Med Chem 38:5031

    Article  CAS  Google Scholar 

  20. Troeberg L, Chen X, Flaherty TM, Morty RE, Cheng M, Hua H, Springer C, McKerrow JH, Kenyon GL, Lonsdale-Eccles JD, Coetzer TH, Cohen FE (2000) Mol Med 6:660

    CAS  Google Scholar 

  21. Opletalova V, Hartl J, Patel A, Palat K, Buchta V (2002) Farmaco 57:135

    Article  CAS  Google Scholar 

  22. Chlupacova M, Opletalova V, Kunes J, Silva L, Buchta V, Duskova L, Kralova K (2005) Folia Pharm Univ Carol XXXIII:31

    Google Scholar 

  23. Opletalova V, Pour M, Kunes J, Buchta V, Silva L, Kralova K, Chlupacova M, Meltrova D, Peterka M, Poslednikova M (2006) Collect Czech Chem Commun 71:44

    Article  CAS  Google Scholar 

  24. Kucerova-Chlupacova M, Kunes J, Buchta V, Vejsova M, Opletalova V (2015) Molecules 20:1104

    Article  Google Scholar 

  25. Lahtchev KL, Batovska DI, Parushev SP, Ubiyvovk VM, Sibirny AA (2008) Eur J Med Chem 43:2220

    Article  CAS  Google Scholar 

  26. Lim SS, Jung SH, Ji J, Shin KH, Keum SR (2000) Chem Pharm Bull 48:1786

    Article  CAS  Google Scholar 

  27. Aida K, Tawata M, Shindo H, Onaya T, Sasaki H, Yamaguchi T, Chin M, Chen ZX, Mitsuhashi H (1990) Planta Med 56:254

    Article  CAS  Google Scholar 

  28. Iwata S, Nagata N, Omae A, Yamaguchi S, Okada Y, Shibata S, Okuyama T (1999) Biol Pharm Bull 22:323

    Article  CAS  Google Scholar 

  29. Blois MS (1958) Nature 181:1199

    Article  CAS  Google Scholar 

  30. Opletalova V, Hartl J, Palat K, Patel A (2000) J Pharm Biomed Anal 23:55

    Article  CAS  Google Scholar 

  31. Yamin LJ, Gasull EI, Blanco SE, Ferretti FH (1998) J Mol Struct Theochem 428:167

    Article  CAS  Google Scholar 

  32. Xue YS, Gong XD (2009) J Mol Struct Theochem 901:226

    Article  CAS  Google Scholar 

  33. Dinya Z, Kiss AI, Pongor G (1978) Acta Chim Acad Sci Hung 98:37

    CAS  Google Scholar 

  34. Ravikumar K, Sridhar B, Aparna P, Rao JM (2005) Acta Crystallogr Sect E Struct Rep Online 61:O1020

    Article  CAS  Google Scholar 

  35. Razak IA, Fun HK, Ngaini Z, Fadzillah SMH, Hussain H (2009) Acta Crystallogr Sect E Struct Rep Online 65:O1133

    Article  Google Scholar 

  36. Razak IA, Fun HK, Ngaini Z, Rahman NIA, Hussain H (2009) Acta Crystallogr Sect E Struct Rep Online 65:O1439

    Article  CAS  Google Scholar 

  37. Ahmad F, Hashim NA, Basar N, Awang K, Ng SW (2011) Acta Crystallogr Sect E Struct Rep Online 67:O2301

    Article  CAS  Google Scholar 

  38. Hashim NA, Ahmad F, Basar N, Awang K, Ng SW (2011) Acta Crystallogr Sect E Struct Rep Online 67:O2300

    Article  CAS  Google Scholar 

  39. Thippeswamy GB, Kumar DV, Jayashree BS, Sridhar MA, Prasad JS (2011) Acta Crystallogr Sect E Struct Rep Online 67:O829

    Article  CAS  Google Scholar 

  40. Zhang Y, Zhang YN, Liu MM, Ryu KC, Ye DY (2011) Acta Crystallogr Sect E Struct Rep Online 67:O912

    Article  CAS  Google Scholar 

  41. Suwunwong T, Chantrapromma S, Pakdeevanich P, Fun HK (2009) Acta Crystallogr Sect E Struct Rep Online 65:01575

    Article  Google Scholar 

  42. Fun HK, Suwunwong T, Anantapong T, Karalai C, Chantrapromma S (2011) Acta Crystallogr Sect E Struct Rep Online 67:O3074

    Article  CAS  Google Scholar 

  43. Sunitha K, Devarajegowda HC, Al-eryani WFA, Prasad YR, Kumar AUM (2012) Acta Crystallogr Sect E Struct Rep Online 68:O61

    Article  CAS  Google Scholar 

  44. Avram SI, Crisan L, Pacureanu LM, Bora A, Seclaman E, Balint M, Kurunczi LG (2013) Med Chem Res 22:3589

    Article  CAS  Google Scholar 

  45. Rastelli G, Antolini L, Benvenuti S, Costantino L (2000) Bioorg Med Chem 8:1151

    Article  CAS  Google Scholar 

  46. Ramunno A, Cosconati S, Sartini S, Maglio V, Angiuoli S, La Pietra V, Di Maro S, Giustiniano M, La Motta C, Da Settimo F, Marinelli L, Novellino E (2012) Eur J Med Chem 51:216

    Article  CAS  Google Scholar 

  47. Oates PJ (2008) Curr Drug Targets 9:14

    Article  CAS  Google Scholar 

  48. Zhang LP, Zhang H, Zhao YN, Li Z, Chen SK, Zhai J, Chen YY, Xie W, Wang Z, Li Q, Zheng XH, Hu XP (2013) FEBS Lett 587:3681

    Article  CAS  Google Scholar 

  49. Wang SJ, Yan JF, Hao D, Niu XW, Cheng MS (2007) Molecules 12:885

    Article  CAS  Google Scholar 

  50. Opletalova V, Patel A, Boulton M, Dundrova A, Lacinova E, Prevorova M, Appeltauerova M, Coufalova M (1996) Collect Czech Chem Commun 61:1093

    Article  CAS  Google Scholar 

  51. Kucerova-Chlupacova M, Opletalova V, Jampilek J, Dolezel J, Dohnal J, Pour M, Kunes J, Vorisek V (2008) Collect Czech Chem Commun 73:1

    Article  CAS  Google Scholar 

  52. Murphy WS, Wattanasin S (1980) J Chem Soc Perkin Trans 1:1567

    Article  Google Scholar 

  53. Seo WD, Kim JH, Kang JE, Ryu HW, Curtis-Long MJ, Lee HS, Yang MS, Park KH (2005) Bioorg Med Chem Lett 15:5514

    Article  CAS  Google Scholar 

  54. Kohler EP, Conant JB (1917) J Am Chem Soc 39:1699

    Article  CAS  Google Scholar 

  55. Black WB, Lutz RE (1953) J Am Chem Soc 75:5990

    Article  CAS  Google Scholar 

  56. Elderfield RC, King TP (1954) J Am Chem Soc 76:5439

    Article  CAS  Google Scholar 

  57. Oh S, Jang S, Kim D, Han I-O, Jung J-C (2006) Arch Pharm Res 29:469

    Article  CAS  Google Scholar 

  58. Stefek M, Snirc V, Djoubissie PO, Majekova M, Demopoulos V, Rackova L, Bezakova Z, Karasu C, Carbone V, El-Kabbani O (2008) Bioorg Med Chem 16:4908

    Article  CAS  Google Scholar 

  59. Shao Y, Molnar LF, Jung Y, Kussmann J, Ochsenfeld C, Brown ST, Gilbert ATB, Slipchenko LV, Levchenko SV, O’Neill DP, DiStasio RA, Lochan RC, Wang T, Beran GJO, Besley NA, Herbert JM, Lin CY, Van Voorhis T, Chien SH, Sodt A, Steele RP, Rassolov VA, Maslen PE, Korambath PP, Adamson RD, Austin B, Baker J, Byrd EFC, Dachsel H, Doerksen RJ, Dreuw A, Dunietz BD, Dutoi AD, Furlani TR, Gwaltney SR, Heyden A, Hirata S, Hsu CP, Kedziora G, Khalliulin RZ, Klunzinger P, Lee AM, Lee MS, Liang W, Lotan I, Nair N, Peters B, Proynov EI, Pieniazek PA, Rhee YM, Ritchie J, Rosta E, Sherrill CD, Simmonett AC, Subotnik JE, Woodcock HL, Zhang W, Bell AT, Chakraborty AK, Chipman DM, Keil FJ, Warshel A, Hehre WJ, Schaefer HF, Kong J, Krylov AI, Gill PMW, Head-Gordon M (2006) Phys Chem Chem Phys 8:3172

    Article  CAS  Google Scholar 

  60. Van Zandt MC, Jones ML, Gunn DE, Geraci LS, Jones JH, Sawicki DR, Sredy J, Jacot JL, DiCioccio AT, Petrova T, Mitschler A, Podjarny AD (2005) J Med Chem 48:3141

    Article  Google Scholar 

  61. Krieger E, Vriend G (2015) J Comput Chem 36:996

    Article  CAS  Google Scholar 

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Acknowledgements

This study was funded by the research program Development and Study of Drugs Progres Q42 (Charles University, Czech Republic), and the VEGA 2/0033/14 and VEGA 2/0041/15 Grants of the Ministry of Education, Science, Research and Sport of the Slovak Republic.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic

    Marta Kucerova-Chlupacova

  2. Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic

    Martin Dosedel

  3. Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic

    Jiri Kunes

  4. Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic

    Marta Soltesova-Prnova, Magdalena Majekova & Milan Stefek

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  1. Marta Kucerova-Chlupacova
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  2. Martin Dosedel
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  4. Marta Soltesova-Prnova
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  5. Magdalena Majekova
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Correspondence to Marta Kucerova-Chlupacova.

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Kucerova-Chlupacova, M., Dosedel, M., Kunes, J. et al. Chalcones and their pyrazine analogs: synthesis, inhibition of aldose reductase, antioxidant activity, and molecular docking study. Monatsh Chem 149, 921–929 (2018). https://doi.org/10.1007/s00706-018-2146-6

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  • DOI: https://doi.org/10.1007/s00706-018-2146-6

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