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Russian Journal of General Chemistry

, Volume 88, Issue 3, pp 541–550 | Cite as

Synthesis, Antibacterial and Antileishmanial Activity, Cytotoxicity, and Molecular Docking of New Heteroleptic Copper(I) Complexes with Thiourea Ligands and Triphenylphosphine

  • A. Saeed
  • F. A. Larik
  • F. Jabeen
  • H. Mehfooz
  • S. A. Ghumro
  • H. R. El-Seedi
  • M. Ali
  • P. A. Channar
  • H. Ashraf
Article

Abstract

A series of copper(I) complexes with triphenylphosphine and N-acyl-N′-arylthioureas were synthesized and characterized by elemental analysis and IR and NMR (1H, 13C, 31P) spectroscopy. The thiourea ligands and their copper(I) triphenylphosphine complexes were screened for antibacterial and antileishmanial activities and cytotoxicity. The synthesized compounds showed much better activity as compared to glucantime and Kanamycin used as reference drugs. The thiourea ligands showed better activity than their Cu(I) complexes. The molecular docking technique was utilized to ascertain the mechanism of action toward molecular targets (GP63 and 16S-rRNA A-site). It was found that the ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces, consistent with the corresponding experimental results. The in silico study of the binding pattern predicted that one of the synthesized ligands, N-(5-chloro-2-nitrophenyl)-N′- pentanoylthiourea, can serve as a potential surrogate for hit-to-lead generation and design of novel antibacterial and antileishmanial agents.

Keywords

thiourea copper(I) complexes triphenylphosphine molecular docking cytotoxicity antileishmanial activity antibacterial activity 

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References

  1. 1.
    Kodomari, M., Suzuki, M., Tanigawa, K., and Aoyama, T., Tetrahedron Lett., 2005, vol. 46, p. 5841. doi 10.1016/j.tetlet.2005.06.135CrossRefGoogle Scholar
  2. 2.
    Batey, R.A. and Powell, D.A., Org Lett., 2000, vol. 2, p. 3237. doi 10.1021/ol006465bCrossRefGoogle Scholar
  3. 3.
    Larik, F.A., Saeed, A., Channar, P.A., Ismail, H., Dilshad, E., and Mirza, B., Bangladesh J. Pharmacol., 2016, vol. 11, p. 894. doi 10.3329/bjp.v11i4.29059CrossRefGoogle Scholar
  4. 4.
    Hartmann, H., Liebscher, J., and Czerney, P., Tetrahedron, 1985, vol. 41, p. 5371. doi 10.1016/S0040-4020(01)96792-4CrossRefGoogle Scholar
  5. 5.
    Cunha, S., Rodrigues, M.T., de Silva, C.C., Jr, Napolitano, H.B., Vencato, I., and Lariucci, C., Tetrahedron, 2005, vol. 61, p. 10536. doi 10.1016/j.tet.2005.08.052CrossRefGoogle Scholar
  6. 6.
    Saeed, A., Flörke, U., and Erben, M.F., J. Sulfur Chem., 2014, vol. 35, p. 318. doi 10.1080/17415993.2013.834904CrossRefGoogle Scholar
  7. 7.
    Larik, F.A., Saeed, A., Channar, P.A., Muqadar, U., Abbas, Q., Hassan, M., Seo, S.Y., and Bolte, M., Eur. J. Med. Chem., 2017, vol. 141, p. 273. doi 10.1016/j.ejmech.2017.09.059CrossRefGoogle Scholar
  8. 8.
    Eweis, M., Elkholy, S.S., and Elsabee, M.Z., Int. J. Biol. Macromol., 2006, vol. 38, p. 1. doi 10.1016/j.ijbiomac.2005.12.009CrossRefGoogle Scholar
  9. 9.
    Sriram, D., Yogeeswari, P., Dinakaran, M., and Thirumurugan, R., J. Antimicrob. Chemother., 2007, vol. 59, p. 1194. doi 10.1093/jac/dkm085CrossRefGoogle Scholar
  10. 10.
    Saeed, A., Shah, M.S., Larik, F.A., Khan, S.U., Channar, P.A., Flörke, U., and Iqbal, J., Med. Chem. Res., 2017, vol. 26, p. 1635. doi 10.1007/s00044-017-1829-6CrossRefGoogle Scholar
  11. 11.
    Saeed, A., Channar, P.A., Larik, F.A., Jabeen, F., Muqadar, U., Saeed, S., Flörke, U., Ismail, H., Dilshad, E., and Mirza, B., Inorg. Chim. Acta, 2017, vol. 464, p. 204. doi 10.1016/j.ica.2017.05.036CrossRefGoogle Scholar
  12. 12.
    Saeed, A., Sajid, R., Channar, P.A., Larik, F.A., Qamar, A., Hassan, M., Raza, H., and Seo, S.-Y., Drug Res. (Stuttgart), 2017, vol. 67, no. 10, p. 596. doi 10.1055/s-0043-113832CrossRefGoogle Scholar
  13. 13.
    Arslan, H., Duran, N., Borekci, G., Koray, O.C., and Akbay, C., Molecules, 2009, vol. 14, p. 519. doi 10.3390/molecules14010519CrossRefGoogle Scholar
  14. 14.
    Park, Y., Harper, K.C., Kuhl, N., Kwan, E.E., Liu, R.Y., and Jacobsen, E.N., Science, 2017, vol. 355, p. 162. doi 10.1126/science.aal1875CrossRefGoogle Scholar
  15. 15.
    Arjunan, V., Anitha, R., Durgadevi, G., Marchewka, M.K., and Mohan, S., J. Mol. Struct., 2017, vol. 1133, p. 187. doi 10.1016/j.molstruc.2016.12.011CrossRefGoogle Scholar
  16. 16.
    Binzet, G., Arslan, H., Florke, U., Kulcu, N., and Duran, N., J. Coord. Chem., 2006, vol. 59, p. 1395. doi 10.1080/00958970500512633CrossRefGoogle Scholar
  17. 17.
    Ugur, D., Arslan, H., and Kulcu, N., Russ. J. Coord. Chem., 2006, vol. 32, p. 669. doi 10.1134/S1070328406090089CrossRefGoogle Scholar
  18. 18.
    Channar, P.A., Saeed, A., Larik, F.A., Rashid, S., Iqbal, Q., Rozi, M., Younis, S., and Mahar, J., Biomed. Pharmacother., 2017, vol. 94, p. 499. doi 10.1016/j.biopha.2017.07.139CrossRefGoogle Scholar
  19. 19.
    Saeed, A., Mahesar, P.A., Channar, P.A., Larik, F.A., Abbas, Q., Hassan, M., Raza, H., and Seo, S.Y., Chem. Biodiversity, 2017, vol. 14, article ID e1700035. doi 10.1002/cbdv.201700035Google Scholar
  20. 20.
    Henderson, W., Nicholson, B.K., Dinger, M.B., and Bennett, R.L., Inorg. Chim. Acta, 2002, vol. 338, p. 218. doi 10.1016/S0020-1693(02)01017-4CrossRefGoogle Scholar
  21. 21.
    Ferreira, M., Assunção, L.S., Silva, A.H., Filippin-Monteiro, F.B., Creczynski-Pasa, T.B., and Sá, M.M., Eur. J. Med. Chem., 2017, vol. 129, p. 151. doi. 10.1016/j.ejmech.2017.02.013CrossRefGoogle Scholar
  22. 22.
    Ozturk, I.I., Yarar, S., Banti, C.N., Kourkoumelis, N., Chrysouli, M.P., Manoli, M., Tasiopoulos, A.J., and Hadjikakou, S.K., Polyhedron, 2017, vol. 123, p. 152. doi 10.1016/j.poly.2016.11.008CrossRefGoogle Scholar
  23. 23.
    Zuckerman, R.L. and Bergman, R.G., Organometallics, 2000, vol. 19, p. 4795. doi 10.1021/om000614cCrossRefGoogle Scholar
  24. 24.
    Channar, P.A., Saeed, A., Albericio, F., Larik, F.A., Abbas, Q., Hassan, M., Raza, H., and Seo, S.Y., Molecules, 2017, vol. 22, p. 1352. doi 10.3390/molecules22081352CrossRefGoogle Scholar
  25. 25.
    Yuan, Y.F., Wang, J.T., Gimeno, M.C., Laguna, A., and Jones, P.G., Inorg. Chim. Acta, 2001, vol. 324, p. 309. doi 10.1016/S0020-1693(01)00661-2CrossRefGoogle Scholar
  26. 26.
    Zhang, Y.M., Wei, T.B., Xian, L., and Gao, L.M., Phosphorus, Sulfur Silicon Relat. Elem., 2004, vol. 179, p. 2007. doi 10.1080/10426500490473456CrossRefGoogle Scholar
  27. 27.
    Goncalves, I.L., de Azambuja, G.O., Kawano, D.F. and Eifler-Lima, V.L., Mini-Rev. Org. Chem., 2018, vol. 15, p. 28. doi 10.2174/1570193X14666170518125219CrossRefGoogle Scholar
  28. 28.
    Saeed, A., Channar, P.A., Larik, F.A., and Flörke, U., Synlett, 2016, vol. 27, p. 1371. doi 10.1055/s-0035-1561848CrossRefGoogle Scholar
  29. 29.
    Saeed, A., Mahesar, P.A., Channar, P.A., Abbas, Q., Larik, F.A., Hassan, M., Raza, H., and Seo, S.-Y., Bioorg. Chem., 2017, vol. 74, p. 187. doi 10.1016/j.bioorg.2017.08.002CrossRefGoogle Scholar
  30. 30.
    Campo, R., Criado, J.J., Garcı́a, E., Hermosa, M.R., Jimenez-Sanchez, A., Manzano, J.L., Monte, E., Rodrıguez-Fernández, E., and Sanz, F., J. Inorg. Biochem., 2002, vol. 89, p. 74. doi 10.1016/S0162-0134 (01)00408-1CrossRefGoogle Scholar
  31. 31.
    Plutín, A.M., Alvarez, A., Mocelo, R., Ramos, R., Castellano, E.E., Silva, M.M., Colina-Vegas, L., Pavan, F.R., and Batista, A.A., Inorg. Chem. Commun., 2016, vol. 63, p. 74. doi 10.1016/j.inoche.2015.11.020CrossRefGoogle Scholar
  32. 32.
    Chetana, P.R., Srinatha, B.S., Somashekar, M.N., and Policegoudra, R.S., J. Mol. Struct., 2016, vol. 1106, p. 352. doi 10.1016/j.molstruc.2015.10.010CrossRefGoogle Scholar
  33. 33.
    Larik, F.A., Saeed, A., Fattah, T.A., Muqadar, U., and Channar, P.A., Appl. Organomet. Chem., 2016, vol. 31, no. 8, article ID e3664. doi 10.1002/aoc.3664Google Scholar
  34. 34.
    Alvar, J., Yactayo, S., and Bern, C., Trends Parasitol., 2006, vol. 22, p. 552. doi 10.1016/j.pt.2006.09.004CrossRefGoogle Scholar
  35. 35.
    Antinori, S., Schifanella, L., and Corbellino, M., Eur. J. Clin. Microbiol., 2012, vol. 31, p. 109. doi 10.1007/s10096-011-1276-0CrossRefGoogle Scholar
  36. 36.
    Chan-Bacab, M.J. and Pena-Rodríguez, L.M., Nat. Prod. Rep., 2001, vol. 18, p. 674. doi 10.1039/B100455GCrossRefGoogle Scholar
  37. 37.
    Faisal, M., Saeed, A., Shahzad, D., Fattah, T.A., Lal, B., Channar, P.A., Mahar, J., Saeed, S., Mahesar, P.A., and Larik, F.A., Eur. J. Med. Chem., 2017, vol. 141, p. 386. doi 10.1016/j.ejmech.2017.10.009CrossRefGoogle Scholar
  38. 38.
    Cars, O., Hedin, A., and Heddini, A., Drug Resist. Updates, 2011, vol. 14, p. 68. doi.org/10.1016/j.drup.2011.02.006CrossRefGoogle Scholar
  39. 39.
    Lai, C.C., Lee, K., Xiao, Y., Ahmad, N., Veeraraghavan, B., Thamlikitkul, V., Tambyah, P.A., Nelwan, R., Shibl, A.M., Wu, J.J., Seto, W.H., and Hsueh, P.R., J. Global Antimicrob. Resist., 2014, vol. 2, p. 141. doi 10.1016/j.jgar.2014.02.007CrossRefGoogle Scholar
  40. 40.
    Woodford, N. and Ellington, M.J., Clin. Microbiol. Infect., 2007, vol. 13, p. 5. doi 10.1111/j.1469-0691.2006.01492.xCrossRefGoogle Scholar
  41. 41.
    Freire-Moran, L., Aronsson, B., Manz, C., Gyssens, I.C., So, A.D., Monnet, D.L., and Cars, O., Drug Resist. Updates, 2011, vol. 14, p. 118. doi 10.1016/j.drup.2011.02.003CrossRefGoogle Scholar
  42. 42.
    Alvan, G., Edlund, C., and Heddini, A., Drug Resist. Updates, 2011, vol. 14, p. 70. doi 10.1016/j.drup.2011.01.007CrossRefGoogle Scholar
  43. 43.
    Wise, R., J. Antimicrob. Chemother., 2011, vol. 66, p. 1939. doi 10.1093/jac/dkr261CrossRefGoogle Scholar
  44. 44.
    Saeed, A., Haroon, M., Muhammad, F., Larik, F.A., Hesham, E.S., and Channar, P.A., J. Organomet. Chem., 2017, vol. 834, p. 88.CrossRefGoogle Scholar
  45. 45.
    Saeed, S., Rashid, N., Jones, P.G., Ali, M., and Hussain, R., Eur. J. Med. Chem., 2010, vol. 45, p. 1323. doi 10.1016/j.ejmech.2009.12.016CrossRefGoogle Scholar
  46. 46.
    Saeed, A., Khurshid, A., Bolte, M., Fantoni, A.C., and Erben, M.F., Spectrochim. Acta, Part A, 2015, vol. 143, p. 59. doi 10.1016/j.saa.2015.02.042CrossRefGoogle Scholar
  47. 47.
    Saeed, A., Shaheen, U., Hameed, A., and Naqvi, S.Z.H., J. Fluorine Chem., 2009, vol. 130, p. 1028. doi 10.1016/j.jfluchem.2009.09.003CrossRefGoogle Scholar
  48. 48.
    Mehfooz, H., Saeed, A., Sharma, A., Albericio, F., Larik, F.A., Jabeen, F., Channar, P.A., and Flörke, U., Crystals, 2017, vol. 7 p. 211. doi 10.3390/cryst7070211Google Scholar
  49. 49.
    Halgren, T.A., J. Comput. Chem., 1996, vol. 17, p. 587. doi 10.1002/(SICI)1096-987X(199604)17:5/6<520:: AID-JCC2>3.0.CO,2-WGoogle Scholar
  50. 50.
    Abdul Fattah, T., Saeed, A., Channar, P.A., Ashraf, Z., Abbas, Q., Hassan, M., and Larik, F.A., Chem. Biol. Drug Des., 2018, vol. 91, p. 434. doi 10.1111/cbdd.13090CrossRefGoogle Scholar
  51. 51.
    Schlagenhauf, E, Etges, R., and Metcalf, P., Structure, 1998, vol. 6, p. 1035. doi 10.1016/S0969-2126(98) 00104-XCrossRefGoogle Scholar
  52. 52.
    Isnard, A., Shio, M.T., and Martin, O., Front. Cell. Infect. Microbiol., 2012, vol. 2, p. 72. doi 10.3389/fcimb.2012.00072CrossRefGoogle Scholar
  53. 53.
    Vicens, Q. and Westhof, E., Structure, 2001, vol. 9, p. 647. doi 10.1016/S0969-2126(01)00629-3CrossRefGoogle Scholar
  54. 54.
    Saeed, A., Khurshid, A., Jasinski, J.P., Pozzi, C.G., Fantoni, A.C., and Erben, M.F., Chem. Phys., 2014, vol. 431, p. 39. doi 10.1016/j.chemphys.2014.01.009CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • A. Saeed
    • 1
  • F. A. Larik
    • 1
  • F. Jabeen
    • 2
  • H. Mehfooz
    • 1
  • S. A. Ghumro
    • 3
  • H. R. El-Seedi
    • 4
  • M. Ali
    • 5
  • P. A. Channar
    • 1
  • H. Ashraf
    • 1
  1. 1.Department of ChemistryQuaid-I-Azam UniversityIslamabadPakistan
  2. 2.Cardiovascular and Metabolic Research UnitLaurentian UniversitySudburyCanada
  3. 3.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan
  4. 4.Division of Pharmacognosy, Department of Medicinal ChemistryUppsala University, Biomedical CenterUppsalaSweden
  5. 5.Department of Biological SciencesQuaid-i-Azam UniversityIslamabadPakistan

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