Skip to main content
SpringerLink
Log in

A novel method for the synthesis and characterization of 10-hexyl-3-(1-hexyl-4, 5-diphenyl-1H-imidazol-2-yl)-10H-phenothiazine: DFT computational, in vitro anticancer and in silico molecular docking studies

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

This study aimed to newly synthesized compound 10-hexyl-3-(1-hexyl-4, 5-diphenyl-1H-imidazol-2-yl)-10H-phenothiazine (abbreviated as HHDIP) by direct and thermal condensation methods, which were characterized by different spectral analysis. The optimized geometry completed the theoretical calculation; the Fourier-transform infrared spectroscopy (FTIR) vibrational frequency studies of HHDIP were found by using the (density functional theory) ab initio calculation with B3LYP/6-311++G (d,p) level. The computed and scaled vibrational frequency values were well matched with the experimental FTIR and Fourier-transform Raman spectroscopy (FT-Raman) spectra. A particular understanding of the FTIR spectra of this title compound was performed by the computed potential energy distribution. The UV–Vis, 1H, and 13C NMR investigations were completed as well as observed; these theoretical outcomes have been seen as in good concurrence with the experimental value. The mass spectroscopy investigation was completed to this compound. In addition to this title compound, the computed (HOMO and LUMO) energy values have been revealed with the charge transfer inside the organic molecules. Nonlinear optics and Mulliken population studies were completed for this title compound. Finally, intensive studies on their anticancer properties were studied through in vitro as well as in silico approaches, suggesting our title compound exhibited tremendous anticancer activity at the concentration value of 250 µg/mL. The in silico docking and adsorption, distribution, metabolisms, excretion and toxicity (ADMET) studies were executed through commercial docking software Discovery Studio, version 4.0 against the protein target c-Met kinase (hepatocyte growth factor; PDB ID: 3F66). The results showed a ligand–receptor interaction energy value of − 64.494 KCal/mol against 3F66 protein (standard anticancer drug tivantinib exhibited − 57.804 KCal/mol). In the ADMET study, it gives good results of nonmutagenic and noncarcinogenic activities. However, in vitro studies exposed more significant antioxidant activity at the range of hydrogen peroxide (H2O2) scavenging activity as 66.31% and 52.877% which showed a vigorous DPPH radical scavenging antioxidant activity concentration value of 500 µg/mL. Further studies are desired to explore its promising anticancer, clinical research and other pharmacological aspects.

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.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20
Fig. 21

Similar content being viewed by others

References

  1. N.P. Desai, V. Trieu, L.Y. Hwang, R. Wu, P. Soon-Shiong, W.J. Gradishar, Anticancer Drugs 19, 899 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. A. Verma, S. Joshi, D. Singh, J. Chem. 2013 (2013)

  3. C. Congiu, M.T. Cocco, V. Onnis, Bioorg. Med. Chem. Lett. 18, 989 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. I.R. Siddiqui, P.K. Singh, V. Srivastava, J. Singh, Indian J. Chem. 49B, 512 (2010)

    CAS  Google Scholar 

  5. B. Narasimhan, D. Sharma, P. Kumar, Med. Chem. Res. 20, 1119 (2011)

    Article  CAS  Google Scholar 

  6. G. Roman, J.G. Riley, J.Z. Vlahakis, R.T. Kinobe, J.F. Brien, K. Nakatsu, W.A. Szarek, Bioorg. Med. Chem. 15, 3225 (2007)

    Article  CAS  PubMed  Google Scholar 

  7. M.A. Babizhayev, Life Sci. 78, 2343 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. P.G. Nantermet, J.C. Barrow, S.R. Lindsley, M. Young, S.S. Mao, S. Carroll, C. Bailey, M. Bosserman, D. Colussi, D.R. McMasters, J.P. Vacca, Bioorg. Med. Chem. Lett. 14, 2141 (2004)

    Article  CAS  PubMed  Google Scholar 

  9. D. Sharma, B. Narasimhan, P. Kumar, V. Judge, R. Narang, E. De Clercq, J. Balzarini, Eur. J. Med. Chem. 44, 2347 (2009)

    Article  CAS  PubMed  Google Scholar 

  10. J.R. Kuma, Pharmacophore. 1, 167 (2010)

    Google Scholar 

  11. H. Bendaha, L. Yu, R. Touzani, R. Souane, G. Giaever, C. Nislow, C. Boone, S. El Kadiri, G.W. Brown, M. Bellaoui, Eur. J. Med. Chem. 46, 4117 (2011)

    Article  CAS  PubMed  Google Scholar 

  12. H.M. Alkahtani, A.Y. Abbas, S. Wang, Bioorg. Med. Chem. Lett. 22, 1317 (2012)

    Article  CAS  PubMed  Google Scholar 

  13. H. Eshghi, M. Rahimizadeh, M. Hasanpour, M. Bakavoli, Res. Chem. Intermed. 41, 4187 (2015)

    Article  CAS  Google Scholar 

  14. Y. Fang, R. Yuan, W.H. Ge, Y.J. Wang, G.X. Liu, M.Q. Li, J.B. Xu, Y. Wan, S.L. Zhou, X.G. Han, P. Zhang, Res. Chem. Intermed. 43, 4413 (2017)

    Article  CAS  Google Scholar 

  15. Y.T. Liu, X.M. Sun, D.W. Yin, F. Yuan, Res. Chem. Intermed. 39, 1037 (2013)

    Article  CAS  Google Scholar 

  16. S.M. Abu-Bakr, F.A. Bassyouni, M.A. Rehim, Res. Chem. Intermed. 38, 2523 (2012)

    Article  CAS  Google Scholar 

  17. S. Zhou, F. Li, P. Zhang, L. Jiang, Res. Chem. Intermed. 39, 1735 (2013)

    Article  CAS  Google Scholar 

  18. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresaman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian Inc., Wallingford CT. 121, 150 (2009)

    Google Scholar 

  19. Z. Özer, J. Iran. Chem. Soc. 10, 1 (2020)

    Google Scholar 

  20. C. Lee, W. Yang, R.G. Parr, Phys. Rev. B. 37, 785 (1988)

    Article  CAS  Google Scholar 

  21. H.B. Schlegal, J. Comput. Chem. 3, 214 (1982)

    Article  Google Scholar 

  22. P.J. Stevens, J.F. Devlin, J.F. Chabalowski, M.J. Frisch, J. Phys. Chem. 98, 11623 (1994)

    Article  Google Scholar 

  23. L.D. Popov, S.I. Levchenkov, I.N. Shcherbakov, G.G. Aleksandrov, Y.P. Tupolova, V.V. Lukov, O.I. Askalepova, V.A. Kogan, J. Struct. Chem. 54, 619 (2013)

    Article  CAS  Google Scholar 

  24. J.I. Ahamed, M. Priya, P. Vinothkumar, K. Sathyamoorthy, P. MuraliManohar, J. Liu, M.F. Valan, J. Mol. Struct. 1202, 127241 (2020)

    Article  CAS  Google Scholar 

  25. A. Frisch, A.B. Neilson, A.J. Holder, Pittsburgh, PA. 566 (2000)

  26. R.F.W. Bader, A Quantum Theory (Clarendon, Oxford, 1990)

    Google Scholar 

  27. R. Bauernschmitt, R. Ahlrichs, Chem. Phys. Lett. 256, 454 (1996)

    Article  CAS  Google Scholar 

  28. E. Kose, A. Atac, M. Karabacak, C. Karaca, M. Eskici, A. Karanfil, Spectrochim. Acta A. 97, 435 (2012)

    Article  CAS  Google Scholar 

  29. R. Ditchfield, J. Chem. Phys. 56, 5688 (1972)

    Article  CAS  Google Scholar 

  30. J. Koska, V.Z. Spassov, A.J. Maynard, L. Yan, N. Austin, P.K. Flook, C.M. Venkatachalam, J. Chem. Inf. Model. 48, 1965 (2008)

    Article  CAS  PubMed  Google Scholar 

  31. M. Arshad, J. Iran. Chem. Soc. 1, 11 (2020)

    Google Scholar 

  32. V.Z. Spassov, P.K. Flook, L. Yan, Protein Eng. Des. Sel. 21, 91 (2008)

    Article  CAS  PubMed  Google Scholar 

  33. M. Karabacak, S. Bilgili, A. Atac, Spectrochim. Acta A. 150, 83 (2015)

    Article  CAS  Google Scholar 

  34. K. Yakushi, I. Ikemoto, H. Kuroda, Acta Cryst. B. 30, 1738 (1974)

    Article  Google Scholar 

  35. Y. Wang, S. Saebar, C.U. Pittman, J. Mol. Struct. (Theochem). 281, 91 (1993)

    Article  Google Scholar 

  36. K. Yakushi, I. Ikemoto, H. Kuroda, Acta Cryst. B. 27, 1710 (1971)

    Article  CAS  Google Scholar 

  37. N.M. O’Boyle, A.L. Tenderholt, K.M. Langner, J. Comput. Chem. 29, 839 (2008)

    Article  PubMed  CAS  Google Scholar 

  38. D. Zhao, K.D. Doney, H. Linnartz, J. Mol. Struct. 296, 1 (2014)

    CAS  Google Scholar 

  39. H. Tanak, Y. Köysal, Y. Ünver, M. Yavuz, S. Isık, K. Sancak, Mol. Phys. 108, 127 (2010)

    Article  CAS  Google Scholar 

  40. S. Sevvanthi, S. Muthu, M. Raja, J. Mol. Struct. 1173, 251 (2018)

    Article  CAS  Google Scholar 

  41. P.J. Brimmer, P.R. Griffiths, Appl. Spectrosc. 42, 242 (1988)

    Article  CAS  Google Scholar 

  42. S. Sakthivel, T. Alagesan, S. Muthu, C.S. Abraham, E. Geetha, J. Mol. Struct. 1156, 645 (2018)

    Article  CAS  Google Scholar 

  43. P.J. Larkin, M.P. Makowski, N.B. Colthup, Spectrochim. Acta A 55, 1011 (1999)

    Article  Google Scholar 

  44. S. Muthu, E.I. Paulraj, Solid State Sci. 14, 476 (2012)

    Article  CAS  Google Scholar 

  45. M. Silverstein, G.C. Basseler, C. Morill, Wiley, New York. (1981)

  46. V. Krishnakumar, R. Ramasamy, Indian J. Pure Appl. Phys. 40, 252 (2002)

    CAS  Google Scholar 

  47. C.S. Hsu, Spectrosc. Lett. 7, 439 (1974)

    Article  CAS  Google Scholar 

  48. B.B. Snider, M.V. Busuyek, Tetrahedron 57, 3301 (2001)

    Article  CAS  Google Scholar 

  49. X. Gao, W. Jiang, G. Jiménez-Osés, M.S. Choi, N.K. Houk, Y.T. Christopher, T. Walsh, Chem. Biol. 20, 870 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. S. Karabuga, S.L. Bars, I. Karakaya, S. Gumus, Tetrahedron Lett. 56, 101 (2015)

    Article  CAS  Google Scholar 

  51. N.B. Patel, J.C. Patel, Arab. J. Chem. 4, 403 (2011)

    Article  CAS  Google Scholar 

  52. D. Sajan, I.H. Joe, V.S. Jayakumar, J. Zaleski, J. Mol. Struct. 785, 43 (2006)

    Article  CAS  Google Scholar 

  53. A. Ben Ahmed, N. Elleuch, H. Feki, Y. Abid, C. Minot, Spectrochim. Acta A. 79, 554 (2011)

    Article  CAS  Google Scholar 

  54. S. Muthu, E.E. Porchelvi, M. Karabacak, A.M. Asiri, S.S. Swathi, J. Mol. Struct. 1081, 400 (2015)

    Article  CAS  Google Scholar 

  55. G. Vengatesh, M. Sundaravadivelu, Res. Chem. Intermed. 45, 4395 (2019)

    Article  CAS  Google Scholar 

  56. M. Raja, R.R. Muhamed, S. Muthu, M. Suresh, J. Mol. Struct. 1128, 481 (2017)

    Article  CAS  Google Scholar 

  57. S.M. Hiremath, A. Suvitha, N.R. Patil, C.S. Hiremath, S.S. Khemalapure, S.K. Pattanayak, V.S. Negalurmath, K. Obelannavar, S.J. Armaković, S. Armaković, Spectrochim. Acta A. 205, 95 (2018)

    Article  CAS  Google Scholar 

  58. N. Subramanian, N. Sundaraganesan, J. Jayabharathi, Spectrochim Acta A. 76, 259 (2010)

    Article  CAS  Google Scholar 

  59. B. Ferah, Anadolu Üniversitesi Bilim Ve Teknoloji Dergisi-B Teorik Bilimler 4, 74 (2016)

    Article  Google Scholar 

  60. G. Gece, Corrosion Sci. 50, 2981 (2008)

    Article  CAS  Google Scholar 

  61. D.F.V. Lewis, C. Ioannides, D.V. Parke, Xenobiotica 24, 401 (1994)

    Article  CAS  PubMed  Google Scholar 

  62. R.G. Pearson, Proc. Natl. Acad. Sci. 83, 8440 (1986)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. B. Fathima Rizwana, J.C. Prasana, S. Muthu, Int. J. Mater. Sci. 12, 196 (2017)

    Google Scholar 

  64. A. Pradhan, S. Vishwakarma, Chem. Int. 6, 224 (2020)

    CAS  Google Scholar 

  65. A. Viji, V. Balachandran, S. Babiyana, B. Narayana, V.V. Saliyan, J. Mol. Struct. 1203, 127452 (2020)

    Article  CAS  Google Scholar 

  66. F. Blanco, I. Alkorta, J. Elguero, Magn. Reson. Chem. 45, 797 (2007)

    Article  CAS  PubMed  Google Scholar 

  67. K. Pihlaja, E. Kleinpeter, Wiley, Hoboken, 17 (1994)

  68. S.C. Yavuz, S. Akkoç, E. Sarıpınar, Synth. Commun. 49, 3198 (2019)

    Article  CAS  Google Scholar 

  69. M.R. Saberi, T.K. Vinh, S.W. Yee, B.N. Griffiths, P.J. Evans, C. Simons, J. Med. Chem. 49, 1016 (2006)

    Article  CAS  PubMed  Google Scholar 

  70. B. Venkatadri, A. Khusro, C. Aarti, M.R. Rameshkumar, P. Agastian, Asian. Pac. J. Trop. Biomed. 7, 782 (2017)

    Article  Google Scholar 

  71. T. Hatano, H. Kagawa, T. Yasuhara, T. Okuda, Chem. Pharm. Bull. 36, 2090 (1988)

    Article  CAS  Google Scholar 

  72. V. Suresh, N. Senthilkumar, R. Thangam, M. Rajkumar, C. Anbazhagan, R. Rengasamy, P. Gunasekaran, S. Kannan, P. Palani, Process Biochem. 48, 364 (2013)

    Article  CAS  Google Scholar 

  73. A.Y. Elnagar, P.W. Sylvester, K.A. El Sayed, Planta Med. 77, 1013 (2011)

    Article  CAS  PubMed  Google Scholar 

  74. W. Tai, T. Lu, H. Yuan, F. Wang, H. Liu, S. Lu, Y. Leng, W. Zhang, Y. Jiang, Y. Chen, J. Mol. Model. 18, 3087 (2012)

    Article  CAS  PubMed  Google Scholar 

  75. C.R. Maroun, T. Rowlands, Pharmacol. Ther. 142, 316 (2014)

    Article  CAS  PubMed  Google Scholar 

  76. L. Ye, X. Ou, Y. Tian, B. Yu, Y. Luo, B. Feng, H. Lin, J. Zhang, S. Wu, Eur. J. Med. Chem. 65, 112 (2013)

    Article  CAS  PubMed  Google Scholar 

  77. C. Li, J.J. Wu, M. Hynes, J. Dosch, B. Sarkar, T.H. Welling, M.P. di Magliano, D.M. Simeone, Gastroenterology 141, 2218 (2011)

    Article  CAS  PubMed  Google Scholar 

  78. P. Daisy, S. Suveena, Asian J. Pharm. Clin. Res. 5, 149 (2012)

    CAS  Google Scholar 

  79. M. Jayakanthan, G. Wadhwa, T.M. Mohan, L. Arul, P. Balasubramanian, D. Sundar, Lett. Drug. Des. Discov. 6, 14 (2009)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are delighted to thank LIFE (Loyola Institute of Frontier Energy) for supporting this study by providing with us laboratory facilities, instrumental facilities and infrastructural facilities. Also thanks to Plant Biology & Biotechnology department, Loyola College (Autonomous), for providing the laboratory facilities of in vitro studies and the Department of Chemistry, Saveetha Engineering College, Thandalam, for supporting this work.

Author information

Authors and Affiliations

  1. Department of Chemistry, LIFE (Loyola Institute of Frontier Energy), Loyola College, University of Madras, Nungambakkam, Chennai, Tamil Nadu, 600034, India

    J. Irshad Ahamed & Mariamichael F. Valan

  2. Department of Science and Humanities, R.M.D Engineering College, Kavaraipettai, Tamil Nadu, 601206, India

    Kamalarajan Pandurengan

  3. Department of Plant Biology and Biotechnology, Loyola College (Autonomous), University of Madras, Chennai, Tamil Nadu, 600 034, India

    Paul Agastian & Babu Venkatadri

  4. Infectious Diseases Laboratory, YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services Hospital Campus, Chennai, Tamil Nadu, 600 113, India

    Marimuthu R. Rameshkumar

  5. Department of Chemistry, Saveetha Engineering College, Thandalam, Chennai, 602 105, India

    Kandaswamy Narendran

Authors
  1. J. Irshad Ahamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariamichael F. Valan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kamalarajan Pandurengan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Agastian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Babu Venkatadri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marimuthu R. Rameshkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kandaswamy Narendran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Irshad Ahamed.

Ethics declarations

Conflict of interest

The authors have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11164_2020_4297_MOESM1_ESM.docx

Supplementary Material includes comparison of experimental and calculated vibational assignments, Mulliken atomic charges, experimental and calculated 1H and 13C NMR chemical shifts assignments and ESI-Mass Spectrum of the HHDIP compound (DOCX 928 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahamed, J.I., Valan, M.F., Pandurengan, K. et al. A novel method for the synthesis and characterization of 10-hexyl-3-(1-hexyl-4, 5-diphenyl-1H-imidazol-2-yl)-10H-phenothiazine: DFT computational, in vitro anticancer and in silico molecular docking studies. Res Chem Intermed 47, 759–794 (2021). https://doi.org/10.1007/s11164-020-04297-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-020-04297-3

Keywords

Search

Navigation