Issue

Vol. 33 No. 9 (2021): Vol 33 Issue 9, 2021

Copyright (c) 2021 AJC

Creative Commons License

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

in vitro DNA Binding, Anticancer and Molecular Docking Studies of New Sydnone Compounds

https://doi.org/10.14233/ajchem.2021.23297
Syed Lidia Hossain
Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore-562157, India
Manoj Mathews
Department of Chemistry, St. Joseph's College (Autonomous), Devagiri, Calicut -673008, India
B. Kirankumar
Department of Biotechnology, SEA College of Science, Commerce and Arts, K.R. Puram, Bangalore-560049, India
C.V. Yelmaggad
Centre for Nano & Soft Matter Science, Bangalore-562162, India
C. Rajendra Singh
Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore-562157, India

Corresponding Author(s) : C. Rajendra Singh

rajendrabiochem@gmail.com

Asian Journal of Chemistry, Vol. 33 No. 9 (2021): Vol 33 Issue 9, 2021

Abstract

Sydnones have been a novel class of mesoionic compound due to versatility of their applications in various fields. Sydnone derivative have seen as an interesting structure grouped in the heterocyclic community, which is having regions of both positive and negative charges linked with a poly-heteroatomic system. This structural characteristic allows them to cross biological membranes and interact with biomolecules. Four sydnones namely 3-(4-decyloxybiphenyl-4′-yl) sydnone (MC-176), 3-(4-octyloxy-2,3-difluorobiphenyl-4′-yl) sydnone (MC-192), 3-(4-biphenyl-4′-yl) sydnone (MC-450) and 3-(4-butylbiphenyl-4′-yl) sydnone (MC-456) were evaluated for biophysical interactions between DNA and sydnones and antiproliferative activity. The UV-visible spectroscopic study indicates interaction between sydnone and dsDNA with a slight red and hypochromic shift in absorption spectra, which shows the intercalation mode of binding. The binding constant of DNA-Sydnone complexes were in the range from 1.4 × 104 M–1 to 7.1 × 104 M–1 for different sydnone compounds (MC-176, MC-192, MC-450, MC-456). FTIR spectra indicated that sydnone interaction with DNA occurs through base pairs and the phosphate backbone of the DNA. The cytotoxic and apoptotic effects of a sydnone derivatives on human cervical cancer (HeLa) and breast tumor (BT) 474 cancer cell lines were determined. The compounds possess antiproliferative activity in a concentration-dependent mode. The changes of morphological characteristic of cancer cells were determined by fluorescent staining techniques indicate the apoptotic cell death. The molecular docking studies of sydnone compounds with caspase 3 and EGF-TK showed better interactions (according to docking score) along with commercially available breast cancer drug molecule anastrozole. The docking score of sydnone molecules (MC-456, MC-450, MC-192 and MC-176) with EGF-TK enzyme were -6.44, -6.42, -5.46 and -4.53, respectively. The binding energy of anastrozole with EGF-TK was -6.41. As well Caspase 3 inhibition with sydnone compounds MC-456, MC-450, MC-192 and MC-176 were -6.09, -6.48, -5 and -3.49, respectively. The binding energy of anastrozole with caspase 3 was -6.24. All sydnone compounds were studied for ADME toxicity studies along with Lipinski rule of five to assess their drug likeness properties by in silico approach. MC-450 found to have good ADMET (absorption, distribution, metabolism, excretion and toxicology) properties among all the sydnone compounds. Thus, the present work indicates that these sydnone compounds would be a well prospective in developing anticancer medicines.

Keywords

Sydnone Liquid crystal Apoptosis Cell lines Molecular docking
Lidia Hossain, S., Mathews, M., Kirankumar, B., Yelmaggad, C., & Rajendra Singh, C. (2021). in vitro DNA Binding, Anticancer and Molecular Docking Studies of New Sydnone Compounds. Asian Journal of Chemistry, 33(9), 2082–2092. https://doi.org/10.14233/ajchem.2021.23297
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal and F. Bray, CA Cancer J. Clin., 71, 209 (2021); https://doi.org/10.3322/caac.21660
  2. J.R. Benson, I. Jatoi, M. Keisch, F.J. Esteva, A. Makris and V.C. Jordan, Lancet, 373, 1463 (2009); https://doi.org/10.1016/S0140-6736(09)60316-0
  3. S. Paul, B. Dash, A.J. Bora and B. Gupta, Int. J. Curr. Pharm. Res., 10, 59 (2018); https://doi.org/10.22159/ijcpr.2018v10i4.28466
  4. C.-C. Tsai, J. Jamison and T. Miller, New Drug Paradigm: Liquid Crystal Pharmaceuticals, Kent State University (2007) https://www.sciencedaily.com/releases/2007/09/070906135516.htm
  5. F. Reinitzer, Liq. Cryst., 9, 421 (1888); https://doi.org/10.1007/BF01516710
  6. L.B. Kier and E.B. Roche, J. Pharm. Sci., 56, 149 (1967); https://doi.org/10.1002/jps.2600560202
  7. U. Fischer and K. Schulze-Osthoff, Pharmacol. Rev., 57, 187 (2005); https://doi.org/10.1124/pr.57.2.6
  8. B. Weber, A. Serafin, J. Michie, C. Van Rensburg, J.C. Swarts and L. Bohm, Anticancer Res., 24(2B), 763 (2004).
  9. S.W. Fesik, Nat. Rev. Cancer, 5, 995 (2005); https://doi.org/10.1038/nrc1776
  10. M. García-Valverde and T. Torroba, Molecules, 10, 318 (2005); https://doi.org/10.3390/10020318
  11. N. Grynberg, T. Gomes, T. Shinzato, A. Echevarria and J. Miller, Anticancer Res., 12, 1025 (1992).
  12. L.E. Mihajlovic, A. Savic, J. Poljarevic, I. Vuèkovic, M. Bulatovic, M. Mojic, D. Maksimovic-Ivanic, S. Mijatovic, G.N. Kaluderovic, S. StosicGrujièic, Ð. Miljkovic, S. Grguric-Šipka and T.J. Sabo, J. Inorg. Biochem., 109, 40 (2012); https://doi.org/10.1016/j.jinorgbio.2012.01.012
  13. A. Caliskan, H. Karadeniz, A. Meric and A. Erdem, Anal. Sci., 26, 117 (2010); https://doi.org/10.2116/analsci.26.117
  14. S.K. Kim and B. Nordén, FEBS Lett., 315, 61 (1993); https://doi.org/10.1016/0014-5793(93)81133-K
  15. B. Nguyen, D. Hamelberg, C. Bailly, P. Colson, J. Stanek, R. Brun, S. Neidle and W. David Wilson, Biophys. J., 86, 1028 (2004); https://doi.org/10.1016/S0006-3495(04)74178-8
  16. S.T. Saito, G. Silva, C. Pungartnik and M. Brendel, J. Photochem. Photobiol. B, 111, 59 (2012); https://doi.org/10.1016/j.jphotobiol.2012.03.012
  17. A. Senff-Ribeiro, A. Echevarria, E.F. Silva, C.R. Franco, S.S. Veiga and M.B. Oliveira, Br. J. Cancer, 91, 297 (2004); https://doi.org/10.1038/sj.bjc.6601946
  18. J. Wang and L. Urban, Drug Discov. World Fall, 5, 73 (2004).
  19. A.P. Li, Drug Discov. Today, 6, 357 (2001); https://doi.org/10.1016/s1359-6446(01)01712-3
  20. S. Usha, I.M. Johnson and R. Malathi, J. Biochem. Mol. Biol., 38, 198 (2005); https://doi.org/10.5483/BMBRep.2005.38.2.198
  21. W. Tian, C. Chen, X. Lei, J. Zhao and J. Liang, Nucleic Acids Res., 46, 363 (2018); https://doi.org/10.1093/nar/gky473
  22. G. Hemamalini, P. Jithesh and P. Nirmala, Int. J. Pharm. Sci. Res., 5, 2374 (2014); https://doi.org/10.13040/IJPSR.0975-8232.5(6).2374-81
  23. T.W. Backman, Y. Cao and T. Girke, Nucleic Acids Res., 9(Web Server issue), W486 (2011); https://doi.org/10.1093/nar/gkr320
  24. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell and A.J. Olson, J. Comput. Chem., 30, 2785 (2009); https://doi.org/10.1002/jcc.21256
  25. S. Salentin, S. Schreiber, V.J. Haupt, M.F. Adasme and M. Schroeder, Nucleic Acids Res., 43, 443 (2015); https://doi.org/10.1093/nar/gkv315
  26. R. Fahrrolfes, S. Bietz, F. Flachsenberg, A. Meyder, E. Nittinger, T. Otto, A. Volkamer and M. Rarey, Nucleic Acids Res., 45, 337 (2017); https://doi.org/10.1093/nar/gkx333
  27. K. Stierand, P.C. Maass and M. Rarey, Bioinformatics, 22, 1710 (2006); https://doi.org/10.1093/bioinformatics/btl150
  28. E. Taillandier and J. Liquier, Methods Enzymol., 211, 307 (1992); https://doi.org/10.1016/0076-6879(92)11018-E
  29. D.M. Loprete and K.A. Hartman, Biochemistry, 32, 4077 (1993); https://doi.org/10.1021/bi00066a032
  30. A.A. Ouameur and H.A. Tajmir-Riahi, J. Biol. Chem., 279, 42041 (2004); https://doi.org/10.1074/jbc.M406053200
  31. D.K. Jangir, S. Charak, R. Mehrotra and S. Kundu, J. Photochem. Photobiol. B, 105, 143 (2011); https://doi.org/10.1016/j.jphotobiol.2011.08.003
  32. M. Tsuboi, Appl. Spectrosc. Rev., 3, 45 (1970); https://doi.org/10.1080/05704927008081687
  33. S. de Almeida, E. Lafayette, L. da Silva, C. Amorim, T. de Oliveira, A. Ruiz, J. de Carvalho, R. de Moura, E. Beltrão, M. de Lima and L. Júnior, Int. J. Mol. Sci., 16, 13023 (2015); https://doi.org/10.3390/ijms160613023
  34. G.S. Kumar, M.A. Ali, T.S. Choon and K.J.R. Prasad, J. Chem. Sci., 128, 391 (2016); https://doi.org/10.1007/s12039-015-1025-5
  35. M. Sirajuddin, S. Ali and A. Badshah, J. Photochem. Photobiol. B, 124, 1 (2013); https://doi.org/10.1016/j.jphotobiol.2013.03.013
  36. S. Nafisi, M. Bonsaii, P. Maali, M.A. Khalil Zadeh and F. Manouchehri, J. Photochem. Photobiol., 100, 84 (2010); https://doi.org/10.1016/j.jphotobiol.2010.05.005
  37. S. Kasibhatla, G.P. Amarante-Mendes, D. Finucane, T. Brunner, E. Bossy-Wetzel and D.R. Green, CSH Protocols, 3, 4493 (2006); https://doi.org/10.1101/pdb.prot4493
  38. M. Ghorab, M.S. Bashandy and M.S. Alsaid, Acta Pharm., 64, 419 (2014); https://doi.org/10.2478/acph-2014-0035
  39. L.F. Galuppo, F.A. dos Reis Lívero, G.G. Martins, C.C. Cardoso, O.C. Beltrame, L.M.B. Klassen, A.V.S. Canuto, A. Echevarria, J.E.Q. Telles, G. Klassen and A. Acco, Basic Clin. Pharmacol. Toxicol., 119, 41 (2016); https://doi.org/10.1111/bcpt.12545
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 1 Download : 1