Skip to main content
SpringerLink
Log in

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

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kodomari, M., Suzuki, M., Tanigawa, K., and Aoyama, T., Tetrahedron Lett., 2005, vol. 46, p. 5841. doi 10.1016/j.tetlet.2005.06.135

    Article  CAS  Google Scholar 

  2. Batey, R.A. and Powell, D.A., Org Lett., 2000, vol. 2, p. 3237. doi 10.1021/ol006465b

    Article  CAS  Google Scholar 

  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.v11i4.29059

    Article  Google Scholar 

  4. Hartmann, H., Liebscher, J., and Czerney, P., Tetrahedron, 1985, vol. 41, p. 5371. doi 10.1016/S0040-4020(01)96792-4

    Article  CAS  Google Scholar 

  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.2005.08.052

    Article  CAS  Google Scholar 

  6. Saeed, A., Flörke, U., and Erben, M.F., J. Sulfur Chem., 2014, vol. 35, p. 318. doi 10.1080/17415993.2013.834904

    Article  CAS  Google Scholar 

  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.2017.09.059

    Article  CAS  Google Scholar 

  8. Eweis, M., Elkholy, S.S., and Elsabee, M.Z., Int. J. Biol. Macromol., 2006, vol. 38, p. 1. doi 10.1016/j.ijbiomac.2005.12.009

    Article  CAS  Google Scholar 

  9. Sriram, D., Yogeeswari, P., Dinakaran, M., and Thirumurugan, R., J. Antimicrob. Chemother., 2007, vol. 59, p. 1194. doi 10.1093/jac/dkm085

    Article  CAS  Google Scholar 

  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/s00044-017-1829-6

    Article  CAS  Google Scholar 

  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.2017.05.036

    Article  CAS  Google Scholar 

  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-0043-113832

    Article  CAS  Google Scholar 

  13. Arslan, H., Duran, N., Borekci, G., Koray, O.C., and Akbay, C., Molecules, 2009, vol. 14, p. 519. doi 10.3390/molecules14010519

    Article  Google Scholar 

  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.aal1875

    Article  CAS  Google Scholar 

  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.2016.12.011

    Article  CAS  Google Scholar 

  16. Binzet, G., Arslan, H., Florke, U., Kulcu, N., and Duran, N., J. Coord. Chem., 2006, vol. 59, p. 1395. doi 10.1080/00958970500512633

    Article  CAS  Google Scholar 

  17. Ugur, D., Arslan, H., and Kulcu, N., Russ. J. Coord. Chem., 2006, vol. 32, p. 669. doi 10.1134/S1070328406090089

    Article  CAS  Google Scholar 

  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.2017.07.139

    Article  CAS  Google Scholar 

  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.201700035

  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)01017-4

    Article  Google Scholar 

  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.2017.02.013

    Article  CAS  Google Scholar 

  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.2016.11.008

    Article  CAS  Google Scholar 

  23. Zuckerman, R.L. and Bergman, R.G., Organometallics, 2000, vol. 19, p. 4795. doi 10.1021/om000614c

    Article  CAS  Google Scholar 

  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/molecules22081352

    Article  Google Scholar 

  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)00661-2

    Article  CAS  Google Scholar 

  26. Zhang, Y.M., Wei, T.B., Xian, L., and Gao, L.M., Phosphorus, Sulfur Silicon Relat. Elem., 2004, vol. 179, p. 2007. doi 10.1080/10426500490473456

    Article  CAS  Google Scholar 

  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 10.2174/1570193X14666170518125219

    Article  Google Scholar 

  28. Saeed, A., Channar, P.A., Larik, F.A., and Flörke, U., Synlett, 2016, vol. 27, p. 1371. doi 10.1055/s-0035-1561848

    Article  CAS  Google Scholar 

  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.2017.08.002

    Article  CAS  Google Scholar 

  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)00408-1

    Article  Google Scholar 

  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.2015.11.020

    Article  Google Scholar 

  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.2015.10.010

    Article  CAS  Google Scholar 

  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.3664

  34. Alvar, J., Yactayo, S., and Bern, C., Trends Parasitol., 2006, vol. 22, p. 552. doi 10.1016/j.pt.2006.09.004

    Article  Google Scholar 

  35. Antinori, S., Schifanella, L., and Corbellino, M., Eur. J. Clin. Microbiol., 2012, vol. 31, p. 109. doi 10.1007/s10096-011-1276-0

    Article  CAS  Google Scholar 

  36. Chan-Bacab, M.J. and Pena-Rodríguez, L.M., Nat. Prod. Rep., 2001, vol. 18, p. 674. doi 10.1039/B100455G

    Article  CAS  Google Scholar 

  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.2017.10.009

    Article  CAS  Google Scholar 

  38. Cars, O., Hedin, A., and Heddini, A., Drug Resist. Updates, 2011, vol. 14, p. 68. doi.org/10.1016/j.drup.2011.02.006

    Article  Google Scholar 

  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.2014.02.007

    Article  Google Scholar 

  40. Woodford, N. and Ellington, M.J., Clin. Microbiol. Infect., 2007, vol. 13, p. 5. doi 10.1111/j.1469-0691.2006.01492.x

    Article  CAS  Google Scholar 

  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.2011.02.003

    Article  Google Scholar 

  42. Alvan, G., Edlund, C., and Heddini, A., Drug Resist. Updates, 2011, vol. 14, p. 70. doi 10.1016/j.drup.2011.01.007

    Article  Google Scholar 

  43. Wise, R., J. Antimicrob. Chemother., 2011, vol. 66, p. 1939. doi 10.1093/jac/dkr261

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.2009.12.016

    Article  CAS  Google Scholar 

  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.2015.02.042

    Article  CAS  Google Scholar 

  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.2009.09.003

    Article  CAS  Google Scholar 

  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/cryst7070211

  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-W

    CAS  Google Scholar 

  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.13090

    Article  CAS  Google Scholar 

  51. Schlagenhauf, E, Etges, R., and Metcalf, P., Structure, 1998, vol. 6, p. 1035. doi 10.1016/S0969-2126(98) 00104-X

    Article  CAS  Google Scholar 

  52. Isnard, A., Shio, M.T., and Martin, O., Front. Cell. Infect. Microbiol., 2012, vol. 2, p. 72. doi 10.3389/fcimb.2012.00072

    Article  Google Scholar 

  53. Vicens, Q. and Westhof, E., Structure, 2001, vol. 9, p. 647. doi 10.1016/S0969-2126(01)00629-3

    Article  CAS  Google Scholar 

  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.2014.01.009

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    A. Saeed, F. A. Larik, H. Mehfooz, P. A. Channar & H. Ashraf

  2. Cardiovascular and Metabolic Research Unit, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada

    F. Jabeen

  3. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    S. A. Ghumro

  4. Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Center, Box 574, SE-751 23, Uppsala, Sweden

    H. R. El-Seedi

  5. Department of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    M. Ali

Authors
  1. A. Saeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. A. Larik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Jabeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Mehfooz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. A. Ghumro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. R. El-Seedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. A. Channar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. Ashraf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Saeed.

Additional information

The text was submitted by the authors in English.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saeed, A., Larik, F.A., Jabeen, F. et al. Synthesis, Antibacterial and Antileishmanial Activity, Cytotoxicity, and Molecular Docking of New Heteroleptic Copper(I) Complexes with Thiourea Ligands and Triphenylphosphine. Russ J Gen Chem 88, 541–550 (2018). https://doi.org/10.1134/S1070363218030246

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363218030246

Keywords

Search

Navigation