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Antimicrobial pyrimidinones II: synthesis and antimicrobial evaluation of certain novel 5,6-disubstituted 2-(substituted amino)alkylthiopyrimidin-4(3H)-ones

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Abstract

A convenient synthesis of certain novel 5,6-disubstituted 2-(substituted amino)alkylthiopyrimidin-4(3H)-ones is reported. 5,6-Disubstituted-2-thiouracils were allowed to react with the appropriate (2-chloroethyl/propyl) amine/imide to give the corresponding 5,6-disubstituted 2-(substituted amino)alkylthiopyrimidin-4(3H)-one derivatives in moderate yields. The antimicrobial potential of the target compounds was determined towards Gram-positive bacteria (Staphylococus aureus, Bacillus subtilis, and Bacillus cereus) and pathogenic fungi (Candida albicans and Aspergillus niger). The obtained data were expressed as diameter of the growth inhibition zone and minimum inhibition concentration (MIC) for the test compounds. The most active compound exhibited dual antibacterial (against S. aureus) and antifungal (against C. albicans) effects with MIC value = 0.0524 µmol/cm3.

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References

  1. Mitsuya H, Yarchoan R, Broder S (1990) Science 249:1533

    Article  CAS  Google Scholar 

  2. Miyasaka T, Tanaka H, Baba M, Hayakawa H, Walker RT, Balzarini J, De Clercq E (1989) J Med Chem 32:2507

    Article  CAS  Google Scholar 

  3. Hopkins AL, Ren J, Tanaka H, Baba M, Okamato M, Stuart DI, Stammers DK (1999) J Med Chem 42:4500

    Article  CAS  Google Scholar 

  4. Novikov MS, Valuev-Elliston VT, Babkov DA, Paramonova MP, Ivanov AV, Gavryushov SA, Khandazhinskaya AL, Kochetkov SN, Pannecouque C, Andrei G, Snoeck R, Balzarini J, Seley-Radtke KL (2013) Bioorg Med Chem 21:1150

    Article  CAS  Google Scholar 

  5. Novikov MS, Babkov DA, Paramonova MP, Khandazhinskaya AL, Ozerov AA, Chizhov AO, Andrei G, Snoeck R, Balzarini J, Seley-Radtke KL (2013) Bioorg Med Chem 21:4151

    Article  CAS  Google Scholar 

  6. Ma T, Pai SB, Zhu YL, Lin JS, Shanmuganathan K, Du J, Wang C, Kim H, Newton MG, Chen YC, Chu CK (1996) J Med Chem 39:2835

    Article  CAS  Google Scholar 

  7. Rahim SG, Trivedi N, B-Batchelor MV, Hardy GW, Mills G, Selway JW, Snowden W, Littler E, Coe PI, Basnak I, Whale RF, Walker RT (1996) J Med Chem 39:789

    Article  CAS  Google Scholar 

  8. McGuigan C, Yarnold CJ, Jones G, Velazquez S, Barucki H, Brancale A, Andrei G, Snoeck R, De Clercq E, Balzarini J (1999) J Med Chem 42:4479

    Article  CAS  Google Scholar 

  9. Guenther S, Balzarini J, De Clercq E, Nair V (2002) J Med Chem 45:5426

    Article  CAS  Google Scholar 

  10. Tsoukala E, Agelis G, Dolinsek J, Botic T, Cencic A, Komiotis D (2007) Bioorg Med Chem 15:3241

    Article  CAS  Google Scholar 

  11. Xie F, Zhao H, Zhao L, Lou L, Hu Y (2009) Bioorg Med Chem Lett 19:275

    Article  CAS  Google Scholar 

  12. Hsu CH, Shen YC, Lin ZZ, Chen PJ, Shao YY, Ding YH, Hsu C, Cheng AL (2010) J Hepatol 53:126

    Article  CAS  Google Scholar 

  13. Manta S, Tsoukala E, Tzioumaki N, Kiritsis C, Balzarini J, Komiotis D (2010) Bioorg Chem 38:48

    Article  CAS  Google Scholar 

  14. Prachayasittikul S, Worachartcheewan A, Nantasenamat C, Chinworrungsee M, Sornsongkhram N, Ruchirawat S, Prachayasittikul V (2011) Eur J Med Chem 46:738

    Article  CAS  Google Scholar 

  15. Mohana KN, Prasanna Kumar BN, Mallesha L (2013) Drug Invent Today 5:216

    Article  CAS  Google Scholar 

  16. Matyugina E, Khandazhinskaya A, Chernousova L, Andreevskaya S, Smirnova T, Chizhov A, Karpenko I, Kochetkov S, Alexandrova L (2012) Bioorg Med Chem 20:6680

    Article  CAS  Google Scholar 

  17. Isobe Y, Tobe M, Inoue Y, Isobe M, Tsuchiya M, Hayashi H (2003) Bioorg Med Chem 11:4933

    Article  CAS  Google Scholar 

  18. Evaldsson C, Ryden I, Uppugunduri S (2007) Int Immunopharmacol 7:1025

    Article  CAS  Google Scholar 

  19. Tobe M, Isobe Y, Goto Y, Obara F, Tsuchiya M, Matsui J, Hirota K, Hayashi H (2000) Bioorg Med Chem 8:2037

    Article  CAS  Google Scholar 

  20. Agarwal A, Srivastava K, Puri SK, Chauhan PM (2005) Bioorg Med Chem 13:6226

    Article  CAS  Google Scholar 

  21. García-Domenech R, López-Peña W, Sanchez-Perdomo Y, Sanders JR, Sierra-Araujo MM, Zapata C, Gálvez J (2008) Int J Pharm 363:78

    Article  Google Scholar 

  22. Bhabak KP, Bhowmick D (2012) J Mol Struct 1022:16

    Article  CAS  Google Scholar 

  23. Sriharsha SN, Satish S, Shashikanth S, Raveesha KA (2006). Bioorg Med Chem 14:7476

    Article  CAS  Google Scholar 

  24. Svenstrup N, Kuhl A, Ehlert K, Habich D (2008) Bioorg Med Chem Lett 18:3215

    Article  CAS  Google Scholar 

  25. Krim J, Grünewald C, Taourirte M, Engels JW (2012) Bioorg Med Chem 20:480

    Article  CAS  Google Scholar 

  26. Al-Abdullah ES, Al-Obaid A-RM, Al-Deeb OA, Habib EE, El-Emam AA (2011) Eur J Med Chem 46:4642

    Article  CAS  Google Scholar 

  27. Semenov V, Voloshina A, Toroptzova E, Kulik N, Zobov V, Giniyatullin RK, Mikhailov A, Nikolaev A, Akamsin V, Reznik V (2006) Eur J Med Chem 41:1093

    Article  CAS  Google Scholar 

  28. Al-Abdullah ES, Al-Turkistani AA, Al-Deeb OA, El-Brollosy NR, Habib EE, El-Emam AA (2014) Drug Res 64:31

    CAS  Google Scholar 

  29. Al-Deeb OA, Al-Turkistani AA, Al-Abdullah ES, El-Brollosy NR, Habib EE, El-Emam AA (2013) Heterocycl Commun 19:411

    Article  CAS  Google Scholar 

  30. Kamdem DP, Gage DA (1995) Planta Med 61:574

    Article  CAS  Google Scholar 

  31. Kim JY, Choi DS, Jung MY (2003) J Agric Food Chem 51:3460

    Article  Google Scholar 

  32. Stanfill SB, Calafat AM, Brown CR, Polzin GM, Chiang JM, Watson CH, Ashley DL (2003) Food Chem Toxicol 41:303

    Article  CAS  Google Scholar 

  33. Jurd L, Narayanan VL, Paull KD (1987) J Med Chem 30:1752

    Article  CAS  Google Scholar 

  34. Leite ACL, Peixoto da Silva K, de Souza IA, Magali de Araújo J, Brondani DJ (2004) Eur J Med Chem 39:1059

    Article  CAS  Google Scholar 

  35. Aboul-Enein MN, El-Azzouny AA, Attia MI, Maklad YA, Amin KM, Abdel-Rehim M, El-Behairy MF (2012) Eur J Med Chem 47:360

    Article  CAS  Google Scholar 

  36. Bang JS, da Oh H, Choi HM, Sur BJ, Lim SJ, Kim JY, Yang HI, Yoo MC, Hahm DH, Kim KS (2009) Arthritis Res Ther 11:R49

    Article  Google Scholar 

  37. Li S, Wang C, Li W, Koike K, Nikaido T, Wang M-W (2007) J Asian Nat Prod Res 9:421

    Article  CAS  Google Scholar 

  38. Taqvi SIH, Shah AJ, Gilani AH (2008) J Cardiovasc Pharmacol 52:452

    Article  CAS  Google Scholar 

  39. Lopes AA, Lopez SN, Regasini LO, Junior JM, Ambrosio DL, Kato MJ, da Silva Bolzani V, Cicarelli RM, Furlan M (2008) Nat Prod Res 22:1040

    Article  CAS  Google Scholar 

  40. Himaja M, Vandana K, Ranjitha A, Ramana M, Karigar A (2011) Int Res J Pharm 2:57

    CAS  Google Scholar 

  41. Sunila E, Kuttan G (2004) J Ethnopharmacol 90:339

    Article  CAS  Google Scholar 

  42. Attia MI, El-Emam AA, Al-Turkistani AA, Kansoh AL, El-Brollosy NR (2014) Molecules 19:279

    Article  Google Scholar 

  43. El-Brollosy NR, Jørgensen PT, Dahan B, Boel AM, Pedersen EB, Nielsen C (2002) J Med Chem 45:5721

    Article  CAS  Google Scholar 

  44. El-Brollosy NR, Pedersen EB, Nielsen C (2003) Arch Pharm Chem Life Sci 336:236

    Article  CAS  Google Scholar 

  45. El-Essawy FA, El-Brollosy NR, Pedersen EB, Nielsen C (2003) J Heterocycl Chem 40:213

    Article  CAS  Google Scholar 

  46. Wamberg M, Pedersen EB, El-Brollosy NR, Nielsen C (2004) Bioorg Med Chem 12:1141

    Article  CAS  Google Scholar 

  47. El-Brollosy NR, Nielsen C, Pedersen EB (2005) Monatsh Chem 136:1247

    Article  CAS  Google Scholar 

  48. Soerensen ER, El-Brollosy NR, Joergensen PT, Pedersen EB, Nielsen C (2005) Arch Pharm Chem Life Sci 338:299

    Article  Google Scholar 

  49. El-Brollosy NR, Sørensen ER, Pedersen EB, Sanna G, La Colla P, Loddo R (2008) Arch Pharm Chem Life Sci 341:9

    Article  CAS  Google Scholar 

  50. El-Brollosy NR, Al-Deeb O, El-Emam AA, Pedersen EB, La Colla P, Collu G, Sanna G, Loddo R (2009) Arch Pharm Chem Life Sci 342:663

    Article  CAS  Google Scholar 

  51. Pedersen EB, Jorgensen PT, Dahan B, El-Brollosy NR, Nielsen C, Boel AM, Vestergaard BF (2003) Preparation of anti-retroviral 5,6-disubstituted acyclo-pyrimidine nucleoside derivatives. PCT International Patent WO 2003057677, Jul 17, 2003; (2003) Chem Abstr 139: 85591

  52. El-Brollosy NR, Al-Omar MA, Al-Deeb OA, El-Emam AA, Nielsen C (2007) J Chem Res 263–267

  53. Feng L, Lv K, Liu M, Wang S, Zhao J, You X, Li S, Cao J, Guo H (2012) Eur J Med Chem 55:125

    Article  CAS  Google Scholar 

  54. Blay G, Cardona L, García B, Lahoz L, Pedro J (1996) Tetrahedron 52:8611

    Article  CAS  Google Scholar 

  55. Fürstner A (1989) Synthesis 1989:571

    Article  Google Scholar 

  56. Aal MTA (2002) Synth Commun 32:1365

    Article  Google Scholar 

  57. Anderson GW, Halverstadt IF, Miller WH, Roblin RO Jr (1945) J Am Chem Soc 67:2197

    Article  CAS  Google Scholar 

  58. Frostick FC Jr, Hauser CR (1949) J Am Chem Soc 71:1350

    Article  CAS  Google Scholar 

  59. Attia MI, El-Brollosy NR, Kansoh AL, Ghabbour HA, Al-Wabli RI, Fun H-K (2014) J Chem 2014:1, article ID 457430

  60. Penna C, Marino S, Gutkind G, Clavin M, Ferraro G, Martino V (1998) J Herbs Spices Med Plants 5:21

    Article  Google Scholar 

  61. Wilkins T, Holdeman LV, Abramson I, Moore W (1972) Antimicrob Agents Chemother 1:451

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the Research Group Project No. RGP-VPP-196.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia

    Mohamed I. Attia & Nasser R. El-Brollosy

  2. Pharmaceutical and Drug Industries Research Division, Medicinal and Pharmaceutical Chemistry Department, National Research Centre, Dokki, Giza, 12622, Egypt

    Mohamed I. Attia

  3. Genetic Engineering and Biotechnology Division, Microbial Chemistry Department, National Research Centre, Dokki, Giza, 12622, Egypt

    Amany L. Kansoh

  4. Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt

    Nasser R. El-Brollosy

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  1. Mohamed I. Attia
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  3. Nasser R. El-Brollosy
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Correspondence to Nasser R. El-Brollosy.

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Attia, M.I., Kansoh, A.L. & El-Brollosy, N.R. Antimicrobial pyrimidinones II: synthesis and antimicrobial evaluation of certain novel 5,6-disubstituted 2-(substituted amino)alkylthiopyrimidin-4(3H)-ones. Monatsh Chem 145, 1825–1837 (2014). https://doi.org/10.1007/s00706-014-1253-2

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  • DOI: https://doi.org/10.1007/s00706-014-1253-2

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