Issue

Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025

Copyright (c) 2025 Mamatha Kasula, DEVENDAR BANOTHU, RAMU GUDA, RAMBABU PALABINDELA, PRABHAKAR MYADARAVENI, RAJASHEKAR KORRA

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

N-Alkylation Hybrids: Synthesis, Characterization, Anticancer Properties and Computational Insights

https://doi.org/10.14233/ajchem.2025.33467
Devendar Banothu
Department of Chemistry, Kakatiya University, Warangal-506009, India
Ramu Guda
Advanced Centre of Research in High Energy Materials (ACRHEM), University of Hyderabad, Hyderabad-500046, India
https://orcid.org/0009-0003-0955-2434
Rambabu Palabindela
Department of Chemistry, Guru Nanak Institutions Technical Campus, Ibrahimpatanam-501506, India
https://orcid.org/0000-0001-9981-3674
Prabhakar Myadaraveni
Department of Chemistry, Kakatiya University, Warangal-506009, India
https://orcid.org/0000-0003-2788-403X
Rajashekar Korra
Department of Chemistry, Kakatiya University, Warangal-506009, India
https://orcid.org/0000-0001-9764-3317
Mamatha Kasula
Department of Chemistry, Kakatiya University, Warangal-506009, India
https://orcid.org/0000-0001-6815-571X

Corresponding Author(s) : Mamatha Kasula

mamathakasula2016@gmail.com

Asian Journal of Chemistry, Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025

Abstract

A series of (E)-2-(2-(anthracen-9-ylmethylene)hydrazinyl)-4-(pyrrolidin-1-ylmethyl)thiazole (7a-l) were synthesized and evaluated for their in vitro anticancer activity against three human cancer cell lines of MCF-7 (breast), A549 (lung) and HepG2 (liver). In this study, cisplatin served as the positive control. The results showed that the synthesized compounds 7c, 7g, 7i, 7j and 7l demonstrated promising activity against all three cancer cell lines. Notably, compound 7j exhibited higher activity than the standard drug cisplatin against MCF-7, A549 and HepG2, with IC50 values of 9.08 ± 0.32 µM, 5.92 ± 1.16 µM and 6.96 ± 0.13 µM, respectively. Molecular docking studies of the compounds 7g, 7i and 7j with DNA topoisomerase II (PDB ID:3QX3) indicated strong affinity toward the target protein. Moreover, an in silico pharmacokinetic profile was generated for compounds 7g, 7i and 7j using SWISS/ADMET and pkCSM. Furthermore, compounds 7g, 7i and 7j were found to comply with the Lipinski, Ghose, Veber, Egan and Muegge rules. Based on the results, compound 7j was characterized by and density functional theory (DFT) studies.

Keywords

Anthracene Thiazole Cyclic secondary amines Anticancer Docking studies DFT studies SWISS-ADMET studies
(1)
Banothu, D.; Guda, R.; Palabindela, R.; Myadaraveni, P.; Korra, R.; Kasula, M. N-Alkylation Hybrids: Synthesis, Characterization, Anticancer Properties and Computational Insights. ajc 2025, 37, 893-908.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. K.P. Rakesh, H.K. Kumara, H.M. Manukumar and D.C. Gowda, Bioorg. Chem., 87, 252 (2019); https://doi.org/10.1016/j.bioorg.2019.03.038
  2. B. Moku, L. Ravindar, K. Rakesh and H.L.J.B.C. Qin, Bioorg. Chem., 86, 513 (2019); https://doi.org/10.1016/j.bioorg.2019.02.030
  3. S. Morgan, P. Grootendorst, J. Lexchin, C. Cunningham and D. Greyson, Health Policy, 100, 4 (2011); https://doi.org/10.1016/j.healthpol.2010.12.002
  4. Y. Chen, L. Liu, L. Xia, N. Wu, Y. Wang, H. Li, X. Chen, X. Zhang, Z. Liu, M. Zhu, Q. Liao and J. Wang, J. Exp. Clin. Cancer Res., 41, 44 (2022); https://doi.org/10.1186/s13046-022-02252-1
  5. U.M. Ammar, M.S. Abdel-Maksoud and C.H. Oh, Eur. J. Med. Chem., 158, 144 (2018); https://doi.org/10.1016/j.ejmech.2018.09.005
  6. F. Gao, X. Zhang, T. Wang and J. Xiao, Eur. J. Med. Chem., 165, 59 (2019); https://doi.org/10.1016/j.ejmech.2019.01.017
  7. I.H. Eissa, A.M. El-Naggar and M.A. El-Hashash, Bioorg. Chem., 67, 43 (2016); https://doi.org/10.1016/j.bioorg.2016.05.006
  8. Y. Pommier, E. Leo, H. Zhang and C. Marchand, Chem. Biol., 17, 421 (2010); https://doi.org/10.1016/j.chembiol.2010.04.012
  9. J.L. Nitiss, Nat. Rev. Cancer, 9, 327 (2009); https://doi.org/10.1038/nrc2608
  10. L.F. Liu, Annu. Rev. Biochem., 58, 351 (1989); https://doi.org/10.1146/annurev.bi.58.070189.002031
  11. M.S. Malik, R.I. Alsantali, R.S. Jassas, A.A. Alsimaree, R. Syed, M.A. Alsharif, K. Kalpana, M. Morad, I.I. Althagafi and S.A. Ahmed, RSC Adv., 11, 35806 (2021); https://doi.org/10.1039/d1ra05686g
  12. M.Z.K. Baig, B. Prusti, S. Bhuin and M. Chakravarty, hosphorus Sulfur Silicon Relat. Elem., 195, 526 (2020); https://doi.org/10.1080/10426507.2020.1723098
  13. I. Kraicheva, E. Vodenicharova, B. Shivachev, R. Nikolova, A. Kril, M. Topashka-Ancheva, I. Iliev, A. Georgieva, T. Gerasimova, T. Tosheva, E. Tashev, I. Tsacheva and K. Troev, Phosphorus Sulfur Silicon Relat. Elem., 188, 1535 (2013); https://doi.org/10.1080/10426507.2012.761986
  14. A. Kastrati, F. Oswald, A. Scalabre and K.M. Fromm, Photochem, 3, 227 (2023); https://doi.org/10.3390/photochem3020015
  15. M. Yoshizawa and J.K. Klosterman, Chem. Soc. Rev., 43, 1885 (2014); https://doi.org/10.1039/C3CS60315F
  16. J. Huang, J.H. Su and H. Tian, J. Mater. Chem., 22, 10977 (2012); https://doi.org/10.1039/c2jm16855c
  17. Meenu, M. Rani and U. Shanker, Environ. Sci.: Adv., 3, 249 (2024); https://doi.org/10.1039/D3VA00245D
  18. C.A. Terry, M.J. Fernández, L. Gude, A. Lorente and K.B. Grant, Biochemistry, 50, 10375 (2011); https://doi.org/10.1021/bi200972c
  19. P. Chinnaayya Swamy, J. Shanmugapriya, S. Singaravadivel, G. Sivaraman and D. Chellappa, ACS Omega, 3, 12341 (2018); https://doi.org/10.1021/acsomega.8b01142
  20. F.A. Holmes, L. Esparza, H.Y. Yap, A.U. Buzdar, R. George, Blumenschein and G.N. Hortobagyi, Cancer Chemother. Pharmacol., 18, 157 (1986); https://doi.org/10.1007/BF00262287
  21. G. Vastag, S. Apostolov and B. Matijevic, Iran. J. Pharm. Res., 17, 100 (2018).
  22. Ü.D. Özkay, Y. Özkay and Ö.D. Can, Med. Chem. Res., 20, 152 (2011); https://doi.org/10.1007/s00044-010-9300-y
  23. T. Ertan, I. Yildiz, S. Ozkan, O. Temiz-Arpaci, F. Kaynak, I. Yalcin, E. Aki-Sener and U. Abbasoglu, Bioorg. Med. Chem., 15, 2032 (2007); https://doi.org/10.1016/j.bmc.2006.12.035
  24. A. Bogdanovic, A. Lazic, S. Grujic, I. Dimkic, S. Stankovic and S. Petrovic, Arh. Hig. Rada Toksikol., 72, 70 (2021); https://doi.org/10.2478/aiht-2021-72-3483
  25. H. Jawed, S.U.A. Shah, S. Jamall and S.U. Simjee, Int. Immunopharmacol., 10, 900 (2010); https://doi.org/10.1016/j.intimp.2010.04.028
  26. M.A. Kaldrikyan, L.A. Grigoryan, R.G. Melik-Ogandzhanyan and F.G. Arsenyan, Pharm. Chem. J., 43, 242 (2009); https://doi.org/10.1007/s11094-009-0287-y
  27. A. Hirashima, Y. Yoshii and M. Eto, Agric. Biol. Chem., 55, 2537 (1991); https://doi.org/10.1080/00021369.1991.10871030
  28. H. Okamoto, S. Kato, T. Kobutani, M. Ogasawara, M. Konnai and T. Takematsu, Agric. Biol. Chem., 55, 2737 (1991); https://doi.org/10.1271/bbb1961.55.2737
  29. F. Zaragoza and H. Stephensen, J. Org. Chem., 64, 2555 (1999); https://doi.org/10.1021/jo982070i
  30. G. Sirasani and R.B. Andrade, Org. Lett., 11, 2085 (2009); https://doi.org/10.1021/ol9004799
  31. A. Ayati, S. Emami, A. Asadipour, A. Shafiee and A. Foroumadi, Eur. J. Med. Chem., 97, 699 (2015); https://doi.org/10.1016/j.ejmech.2015.04.015
  32. M. Djukic, M. Fesatidou, I. Xenikakis, A. Geronikaki, V.T. Angelova, V. Savic, M. Pasic, B. Krilovic, D. Djukic, B. Gobeljic, M. Pavlica, A. Djuric, I. Stanojevic, D. Vojvodic and L. Saso, Chem. Biol. Interact., 286, 119 (2018); https://doi.org/10.1016/j.cbi.2018.03.013
  33. R.N. Sharma, F.P. Xavier, K.K. Vasu, S.C. Chaturvedi and S.S. Pancholi, J. Enzyme Inhib. Med. Chem., 24, 890 (2009); https://doi.org/10.1080/14756360802519558
  34. S. Bondock, T. Naser and Y.A. Ammar, Eur. J. Med. Chem., 62, 270 (2013); https://doi.org/10.1016/j.ejmech.2012.12.050
  35. C.I. Lino, I. Goncalves de Souza, B.M. Borelli, T.T. Silvério Matos, I.N. Santos Teixeira, J.P. Ramos, E. Maria de Souza Fagundes, P. de Oliveira Fernandes, V.G. Maltarollo, S. Johann and R.B. de Oliveira, Eur. J. Med. Chem., 151, 248 (2018); https://doi.org/10.1016/j.ejmech.2018.03.083
  36. H. Osman, S.K. Yusufzai, M.S. Khan, B.M. Abd Razik, O. Sulaiman, S. Mohamad, J.A. Gansau, M.O. Ezzat, T. Parumasivam and M.Z. Hassan, J. Mol. Struct., 1166, 147 (2018); https://doi.org/10.1016/j.molstruc.2018.04.031
  37. N. Ahangar, A. Ayati, E. Alipour, A. Pashapour, A. Foroumadi and S. Emami, Chem. Biol. Drug Des., 78, 844 (2011); https://doi.org/10.1111/j.1747-0285.2011.01211.x
  38. C.B. Mishra, S. Kumari and M. Tiwari, Eur. J. Med. Chem., 92, 1 (2015); https://doi.org/10.1016/j.ejmech.2014.12.031
  39. Leoni A, Locatelli A, Morigi R, Rambaldi M, Expert Opin. Ther. Patents, 24, 201 (2014); https://doi.org/10.1517/13543776.2014.858121
  40. P.C. Sharma, K.K. Bansal, A. Sharma, D. Sharma and A. Deep, Eur. J. Med. Chem., 188, 112016 (2020); https://doi.org/10.1016/j.ejmech.2019.112016
  41. A. Puszkiel, G. Noé, A. Bellesoeur, N. Kramkimel, M.-N. Paludetto, A. Thomas-Schoemann, M. Vidal, F. Goldwasser, E. Chatelut and B. Blanchet, Clin. Pharmacokinet., 58, 451 (2019); https://doi.org/10.1007/s40262-018-0703-0
  42. G.M. Keating, Drugs, 77, 85 (2017); https://doi.org/10.1007/s40265-016-0677-x
  43. Anuradha, S. Patel, R. Patle, P. Parameswaran, A. Jain and A. Shard, Eur. J. Pharm. Sci., 134, 20 (2019); https://doi.org/10.1016/j.ejps.2019.04.005
  44. Y. Wang, S.W. Chen, G. Hu, J. Wang, W.F. Gou, D.Y. Zuo, Y.C. Gu, P. Gong and X. Zhai, Eur. J. Med. Chem., 143, 123 (2018); https://doi.org/10.1016/j.ejmech.2017.11.008
  45. S.J. Yao, Z.H. Ren, Y.Y. Wang and Z.H. Guan, J. Org. Chem., 81, 4226 (2016); https://doi.org/10.1021/acs.joc.6b00580
  46. E. Lacivita, M. Leopoldo, P.D. Giorgio, F. Berardi and R. Perrone, Bioorg. Med. Chem., 17, 1339 (2009); https://doi.org/10.1016/j.bmc.2008.12.015
  47. R. Maia, R. Tesch and C. Fraga, Expert Opin. Ther. Pat., 22, 1169 (2012); https://doi.org/10.1517/13543776.2012.719878
  48. S.G. O’Brien, F. Guilhot, R.A. Larson, I. Gathmann, M. Baccarani, F. Cervantes, J.J. Cornelissen, T. Fischer, A. Hochhaus, T. Hughes, K. Lechner, J.L. Nielsen, P. Rousselot, J. Reiffers, G. Saglio, J. Shepherd, B. Simonsson, A. Gratwohl, J.M. Goldman, H. Kantarjian, K. Taylor, G. Verhoef, A.E. Bolton, R. Capdeville and B.J. Druker, N. Engl. J. Med., 348, 994 (2003); https://doi.org/10.1056/NEJMoa022457
  49. A. Morikawa and N.L. Henry, Clin. Cancer Res., 21, 3591 (2015); https://doi.org/10.1158/1078-0432.CCR-15-0390
  50. C. Pavlovsky, O. Chan, C. Talati and J. Pinilla-Ibarz, Future Oncol., 15, 257 (2019); https://doi.org/10.2217/fon-2018-0371
  51. P. Anand and B. Singh, Mini Rev. Med. Chem., 14, 623 (2014); https://doi.org/10.2174/1389557514999140728102737
  52. S. Routier, J.L. Bernier, J.P. Catteau, J.F. Riou and C. Bailly, Anticancer Drug Des., 13, 407 (1998).
  53. P. De Isabella, M. Palumbo, C. Sissi, N. Carenini, G. Capranico, E. Menta, A. Oliva, S. Spinelli, A.P. Krapcho, F.C. Giuliani and F. Zunino, Biochem. Pharmacol., 53, 161 (1997); https://doi.org/10.1016/S0006-2952(96)00646-6
  54. A.H. Abdullah, N.S. Ibrahim, F.K. Algethami, A.H. Elwahy, I.A. Abdelhamid and M.E. Salem, J. Mol. Struct., 1302, 137506 (2024); https://doi.org/10.1016/j.molstruc.2024.137506
  55. E.T. Warda, I.A. Shehata, M.B. El-Ashmawy and N.S. El-Gohary, Bioorg. Med. Chem., 28, 115674 (2020); https://doi.org/10.1016/j.bmc.2020.115674
  56. T. Khan, K. Sankhe, V. Suvarna, A. Sherje, K. Patel and B. Dravyakar, Biomed. Pharmacother., 103, 923 (2018); https://doi.org/10.1016/j.biopha.2018.04.021
  57. M.S. Sinicropi, J. Ceramella, P. Vanelle, D. Iacopetta, O. Khoumeri, C. Rosano, S. Abdelmohsen, W. Abdelhady and H. El-Kashef, Pharmaceuticals, 16, 946 (2023); https://doi.org/10.3390/ph16070946
  58. A.K. McClendon and N. Osheroff, Mutat. Res., 623, 83 (2007); https://doi.org/10.1016/j.mrfmmm.2007.06.009
  59. R. Gali, J. Banothu, M. Porika, R. Velpula, R. Bavantula and S. Abbagani, RSC Adv., 4, 53812 (2014); https://doi.org/10.1039/C4RA11428K
  60. V. Unadkat, S. Rohit, P. Parikh, K. Patel, V. Sanna and S. Singh, OncoTargets Ther., 2, 479 (2022); https://doi.org/10.2147/OTT.S357765
  61. http://autodock.scripps.edu/resources/references
  62. Discovery Studio Modeling Environment, Release 4.1.0, Accelrys Software Inc.: San Diego, California, USA (2013).
  63. A.D. Becke, J. Chem. Phys., 98, 5648 (1993); https://doi.org/10.1063/1.464913
  64. C. Lee, W. Yang and R.G. Parr, Phys. Rev. B Condens. Matter, 37, 785 (1988); https://doi.org/10.1103/PhysRevB.37.785
  65. N. Kavitha, M. Alivelu and T. Savithajyostna, Chem. Phys. Impact, 8, 100602 (2024); https://doi.org/10.1016/j.chphi.2024.100602
  66. C.C. Wu, T.K. Li, L. Farh, L.Y. Lin, T.S. Lin, Y.J. Yu, Y. Tj, C.W. Chiang and N.L. Chan, Science, 333, 459 (2011); https://doi.org/10.1126/science.1204117
  67. C.C. Wu, T.K. Li, L. Farh, L.-Y. Lin, T.-S. Lin, Y.-J. Yu, T.-J. Yen, C.-W. Chiang and N.-L. Chan, Science, 333, 459 (2011); https://doi.org/10.1126/science.1204117
  68. R. Palabindela, R. Guda, G. Ramesh, P. Myadaraveni, D. Banothu, G. Ravi, R. Korra, H. Mekala and M. Kasula, J. Heterocycl. Chem., 59, 1533 (2022); https://doi.org/10.1002/jhet.4488
  69. Y.B. Shankar Rao, M.V.S. Prasad, N. Udaya Sri and V. Veeraiah, J. Mol. Struct., 1108, 567 (2016); https://doi.org/10.1016/j.molstruc.2015.12.008
  70. B.S. Iyengar, R.T. Dorr, D.S. Alberts, A.M. Sólyom, M. Krutzsch and W.A. Remers, J. Med. Chem., 40, 3734 (1997); https://doi.org/10.1021/jm970308+
  71. X. Zhang, Z. Chi, J. Zhang, H. Li, B. Xu, X. Li, S. Liu, Y. Zhang and J. Xu, J. Phys. Chem. B, 115, 7606 (2011); https://doi.org/10.1021/jp202112e
  72. M. Manju, S. Suresh, P.A. Vivekanand, S. Gunasekaran, S. Srinivasan and C.S. Biju, Mater. Today Proc., 36, 857 (2021); https://doi.org/10.1016/j.matpr.2020.07.018
  73. M. Pramanik, N. Chatterjee, S. Das, K.D. Saha and A. Bhaumik, Chem. Commun., 49, 9461 (2013); https://doi.org/10.1039/c3cc44989k
  74. M. Govindarajan, M. Karabacak, V. Udayakumar and S. Periandy, Spectrochim. Acta A Mol. Biomol. Spectrosc., 88, 37 (2012); https://doi.org/10.1016/j.saa.2011.11.052
  75. A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  76. M.J. Waring, J. Arrowsmith, A.R. Leach, P.D. Leeson, S. Mandrell, R.M. Owen, G. Pairaudeau, W.D. Pennie, S.D. Pickett, J. Wang, O. Wallace and A. Weir, Nat. Rev. Drug Discov., 14, 475 (2015); https://doi.org/10.1038/nrd4609
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download
PDF
Statistic
Read Counter : 211 Download : 181
PlumX