Issue

Vol. 36 No. 5 (2024): Vol 36 Issue 5, 2024

Copyright (c) 2024 Ganesh Sonawane, Shweta Sharma, Ritu Gilhotra

Creative Commons License

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

In silico Analysis of 1,3,4-Oxadiazoles as Potential BCL-2 Inhibitor for Cancer Treatment

https://doi.org/10.14233/ajchem.2024.31342
Ganesh Sonawane
Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur-302017, India
https://orcid.org/0000-0002-5755-8713
Shweta Sharma
Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur-302017, India
https://orcid.org/0009-0008-7324-4328
Ritu Gilhotra
Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur-302017, India
https://orcid.org/0000-0003-2736-4886

Corresponding Author(s) : Ganesh Sonawane

gbsonawane8@gmail.com

Asian Journal of Chemistry, Vol. 36 No. 5 (2024): Vol 36 Issue 5, 2024

Abstract

The possible efficacy of 1,3,4-oxadiazoles as B-cell lymphoma 2 (BCL-2) inhibitors for cancer treatment is investigated in this study using in silico approaches such as molecular docking, ADME and toxicity prediction. Molecular docking studies predict the binding affinities and binding modes of a series of 1,3,4-oxadiazole derivatives with the BCL-2 protein. The results revealed that the compounds with strong interactions and favourable binding modes, indicating their potential as BCL-2 inhibitors. An ADMET analysis assesses the pharmacokinetic properties and potential toxicity of the identified compounds. Parameters such as absorption, distribution, metabolism, excretion and toxicity (ADMET) were evaluated to predict the suitability of these 1,3,4-oxadiazoles as drug candidates for cancer therapy. The integration of molecular docking and ADMET analysis data led to the identification and prioritization of lead compounds with potent BCL-2 inhibitory activity and favourable pharmacokinetic profiles. This research contributes to the on-going efforts in drug discovery, emphasizing the potential of 1,3,4-oxadiazoles as a class of compounds with significant anticancer properties through BCL-2 inhibition.

Keywords

1,3,4-Oxadiazoles Cancer BCL-2 Molecular docking ADMET analysis ProTox-II
Sonawane, G., Sharma, S., & Gilhotra, R. (2024). In silico Analysis of 1,3,4-Oxadiazoles as Potential BCL-2 Inhibitor for Cancer Treatment. Asian Journal of Chemistry, 36(5), 1072–1088. https://doi.org/10.14233/ajchem.2024.31342
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. J.M. Adams and S. Cory, Oncogene, 26, 1324 (2007); https://doi.org/10.1038/sj.onc.1210220
  2. R.J. Youle and A. Strasser, Nat. Rev. Mol. Cell Biol., 9, 47 (2008); https://doi.org/10.1038/nrm2308
  3. D. Hanahan and R.A. Weinberg, Cell, 144, 646 (2011); https://doi.org/10.1016/j.cell.2011.02.013
  4. R. Hamdy, S.A. Elseginy, N.I. Ziedan, M. El-Sadek, E. Lashin, A.T. Jones and A.D. Westwell, Int. J. Mol. Sci., 21, 8980 (2020); https://doi.org/10.3390/ijms21238980
  5. A.R. Delbridge and A. Strasser, Cell Death Differ., 22, 1071 (2015); https://doi.org/10.1038/cdd.2015.50
  6. S. Cory and J.M. Adams, Nat. Rev. Cancer, 2, 647 (2002); https://doi.org/10.1038/nrc883
  7. F. Marra, A. Gastaldelli, G. Svegliati Baroni, G. Tell and C. Tiribelli, Trends Mol. Med., 14, 72 (2008); https://doi.org/10.1016/j.molmed.2007.12.003
  8. T. Oltersdorf, S.W. Elmore, A.R. Shoemaker, R.C. Armstrong, D.J. Augeri, B.A. Belli, M. Bruncko, T.L. Deckwerth, J. Dinges, P.J. Hajduk, M.K. Joseph, S. Kitada, S.J. Korsmeyer, A.R. Kunzer, A. Letai, C. Li, M.J. Mitten, D.G. Nettesheim, S.C. Ng, P.M. Nimmer, J.M. O’Connor, A. Oleksijew, A.M. Petros, J.C. Reed, S.K. Tahir, C.B. Thompson, K.J. Tomaselli, W. Shen, B. Wang, M.D. Wendt, H. Zhang, S.W. Fesik and S.H. Rosenberg, Nature, 435, 677 (2005); https://doi.org/10.1038/nature03579
  9. M. Vogler, Cell Death Differ., 19, 67 (2012); https://doi.org/10.1038/cdd.2011.158
  10. J.C. Reed, Cell Death Differ., 13, 1378 (2006); https://doi.org/10.1038/sj.cdd.4401975
  11. A. Das, M. Sarangi, K. Jangid, V. Kumar, A. Kumar, P.P. Singh, K. Kaur, V. Kumar, S. Chakraborty and V. Jaitak, J. Biomol. Struct. Dyn., (2024);https://doi.org/10.1080/07391102.2023.2256876
  12. T.A. Yousef, A.G. Alhamzani, M.M. Abou-Krisha, G. Kanthimathi, M.S. Raghu, K.Y. Kumar, M.K. Prashanth and B.H. Jeon, Heliyon, 9, e13460 (2023); https://doi.org/10.1016/j.heliyon.2023.e13460
  13. K. Patil, M. Nemade, A. Bedse, P. Bedse, R. Ranjan, H. Tare and M. Bedse, Int. J. Drug Deliv. Technol., 13, 966 (2023); https://doi.org/10.25258/ijddt.13.3.31
  14. S. Nayak, S.L. Gaonkar, E.A. Musad and A.M.A.L. Dawsar, J. Saudi Chem. Soc., 25, 101284 (2021); https://doi.org/10.1016/j.jscs.2021.101284
  15. Y. Ono, M. Ninomiya, D. Kaneko, A.D. Sonawane, T. Udagawa, K. Tanaka, A. Nishina and M. Koketsu, Bioorg. Chem., 104, 104245 (2020); https://doi.org/10.1016/j.bioorg.2020.104245
  16. A. Tiwari, N.G. Kutty, N. Kumar, A. Chaudhary, P.V. Raj, R. Shenoy, and C. Mallikarjuna Rao, Cytotechnology, 68, 2553 (2016); https://doi.org/10.1007/s10616-016-9979-9
  17. A. Daina, O. Michielin and V. Zoete, J. Chem. Inf. Model., 54, 3284 (2014); https://doi.org/10.1021/ci500467k
  18. G. Skoraczyñski, M. Kitlas, B. Miasojedow and A. Gambin, J. Cheminform., 15, 6 (2023); https://doi.org/10.1186/s13321-023-00678-z
  19. Y. Ono, M. Ninomiya, D. Kaneko, A.D. Sonawane, T. Udagawa, K. Tanaka, A. Nishina and M. Koketsu, Bioorg. Chem., 104, 104245 (2020); https://doi.org/10.1016/j.bioorg.2020.104245
  20. M. Soleiman-Beigi, R. Aryan, M. Yousofizadeh and S. Khosravi, J. Chem., 2013, 476358 (2013); https://doi.org/10.1155/2013/476358
  21. A.K. Nagariya, A.K. Meena, S. Kumar, R. Singh, A.K. Yadav and U.S. Niranjan, J. Pharm. Res., 3, 451 (2010).
  22. S. Rochlani, M. Bhatia, S. Rathod, P. Choudhari and R. Dhavale, Nat. Prod. Res., 38, 891 (2023); https://doi.org/10.1080/14786419.2023.2202398
  23. A. Drefahl, J. Cheminform., 3, 1 (2011); https://doi.org/10.1186/1758-2946-3-1
  24. S. Dallakyan and A.J. Olson, Methods Mol. Biol., 1263, 243 (2015); https://doi.org/10.1007/978-1-4939-2269-7_19
  25. A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  26. D.E.V. Pires, T.L. Blundell and D.B. Ascher, J. Med. Chem., 58, 4066 (2015); https://doi.org/10.1021/acs.jmedchem.5b00104
  27. S. Rathod, K. Shinde, J. Porlekar, P. Choudhari, R. Dhavale, D. Mahuli, Y. Tamboli, M. Bhatia, K.P. Haval, A.G. Al-Sehemi and M. Pannipara, ACS Omega, 8, 391 (2023); https://doi.org/10.1021/acsomega.2c04837
  28. A.J. Souers, J.D. Leverson, E.R. Boghaert, S.L. Ackler, N.D. Catron, J. Chen, B.D. Dayton, H. Ding, S.H. Enschede, W.J. Fairbrother, D.C.S. Huang, S.G. Hymowitz, S. Jin, S.L. Khaw, P.J. Kovar, L.T. Lam, J. Lee, H.L. Maecker, K.C. Marsh, K.D. Mason, M.J. Mitten, P.M. Nimmer, A. Oleksijew, C.H. Park, C.-M. Park, D.C. Phillips, A.W. Roberts, D. Sampath, J.F. Seymour, M.L. Smith, G.M. Sullivan, S.K. Tahir, C. Tse, M.D. Wendt, Y. Xiao, J.C. Xue, H. Zhang, R.A Humerickhouse, S.H. Rosenberg and S.W. Elmore, Nat. Med., 19, 202 (2013); https://doi.org/10.1038/nm.3048
  29. M. Wiederstein and M.J. Sippl, Nucleic Acids Res., 35(Web Server), W407 (2007); https://doi.org/10.1093/nar/gkm290
  30. M.J. Sippl, Proteins, 17, 355 (1993); https://doi.org/10.1002/prot.340170404
  31. R. Lüthy, J.U. Bowie and D. Eisenberg, Nature, 356, 83 (1992); https://doi.org/10.1038/356083a0
  32. A. Singh, R. Kaushik, A. Mishra, A. Shanker and B. Jayaram, Biochim. Biophys. Acta, Proteins Proteom., 1864, 11 (2016); https://doi.org/10.1016/j.bbapap.2015.10.004
  33. R. Gaikwad, S. Rathod and A. Shinde, Asian J. Pharm. Res., 12, 267 (2022); https://doi.org/10.52711/2231-5691.2022.00043
  34. S. Rathod, P. Chavan, D. Mahuli, S. Rochlani, S. Shinde, S. Pawar, P. Choudhari, R. Dhavale, P. Mudalkar and F. Tamboli, J. Mol. Model., 29, 113 (2023); https://doi.org/10.1007/s00894-023-05521-8
  35. V.K. Bagal, S.S. Rathod, M.M. Mulla, S.C. Pawar, P.B. Choudhari, V.T. Pawar and D.V. Mahuli, Nat. Prod. Res., 37, 4053 (2023); https://doi.org/10.1080/14786419.2023.2165076
  36. S. Forli, R. Huey, M.E. Pique, M.F. Sanner, D.S. Goodsell and A.J. Olson, Nat. Protoc., 11, 905 (2016); https://doi.org/10.1038/nprot.2016.051
  37. P. Banerjee, O.A. Eckert, A.K. Schrey and R. Preissner, Nucleic Acids Res., 46(W1), W257 (2018); https://doi.org/10.1093/nar/gky318
  38. P. Banerjee, F.O. Dehnbostel and R. Preissner, Front. Chem., 6, 362 (2018); https://doi.org/10.3389/fchem.2018.00362
  39. M.N. Drwal, P. Banerjee, M. Dunkel, M.R. Wettig and R. Preissner, Nucleic Acids Res., 42(Web Server), W53 (2014); https://doi.org/10.1093/nar/gku401
  40. R.A. Laskowski, M.W. MacArthur, D.S. Moss and J.M. Thornton, J. Appl. Cryst., 26, 283 (1993); https://doi.org/10.1107/S0021889892009944
  41. R.A. Laskowski, J.A.C. Rullmann, M.W. MacArthur, R. Kaptein and J.M. Thornton, J. Biomol. NMR, 8, 477 (1996); https://doi.org/10.1007/BF00228148
  42. R.A. Laskowski, M.W. MacArthur and J.M. Thornton, in eds.: M.G. Rossmann and E. Arnold, PROCHECK: Validation of Protein Structure Coordinates, In: International Tables of Crystallography, Volume F. Crystallography of Biological Macromolecules, Dordrecht, Kluwer Academic Publishers, The Netherlands, pp. 722-725 (2001).
  43. A.L. Morris, M.W. MacArthur, E.G. Hutchinson and J.M. Thornton, Proteins, 12, 345 (1992); https://doi.org/10.1002/prot.340120407
  44. J.U. Bowie, R. Lüthy and D. Eisenberg, Science, 253, 164 (1991); https://doi.org/10.1126/science.1853201
  45. M. Wiederstein and M.J. Sippl, Nucleic Acids Res., 35(Suppl. 2), W407 (2007); https://doi.org/10.1093/nar/gkm290
  46. D.B. Kitchen, H. Decornez, J.R. Furr and J. Bajorath, Nat. Rev. Drug Discov., 3, 935 (2004); https://doi.org/10.1038/nrd1549
  47. R. Wang and S. Wang, J. Chem. Inf. Comput. Sci., 41, 1422 (2001); https://doi.org/10.1021/ci010025x
Read More
Author biographies is not available.
Statistic
Read Counter : 0 Download : 0