Issue

Vol. 37 No. 1 (2025): Vol 37 Issue 1, 2025

Copyright (c) 2024 Winfred J John, Pushpam

Creative Commons License

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

DFT, Wave Function and SAR Analyses of Fexinidazole: A Drug for Sleeping Sickness

https://doi.org/10.14233/ajchem.2025.32847
E. Jimla Pushpam
Department of Chemistry, St. John’s College (Affiliated to Manonmaniam Sundaranar University, Abishekapatti), Palayamkottai, Tirunelveli-627002, India
https://orcid.org/0000-0003-1821-1511
J. Winfred Jebaraj
Department of Chemistry, St. John’s College (Affiliated to Manonmaniam Sundaranar University, Abishekapatti), Palayamkottai, Tirunelveli-627002, India
https://orcid.org/0000-0001-8731-806X

Corresponding Author(s) : J. Winfred Jebaraj

winfred.chem@stjohnscollege.edu

Asian Journal of Chemistry, Vol. 37 No. 1 (2025): Vol 37 Issue 1, 2025

Abstract

Fexinidazole is a newly authorized drug employed for the treatment of sleeping sickness in South Africa. The characteristics of drug molecule in the gaseous form were calculated using Gaussian 16W software, employing the DFT/B3LYP/6-311++G(d,p) level of theory. The absence of imaginary frequency indicates the full convergence and optimization. Mulliken charge analysis was carried out. The ESP elucidates the suitability of the nitro group for electrophilic assault and FMO demonstrates that it is an electron donor. The NLO investigation reveals that it is a good NLO candidate and the NBO studies reveals that it is highly stable. The NCI interaction demonstrates that it exhibits van der Waals and steric repulsion forces. IFCT, STM and aromaticity determinations were performed. The S0 → S3 and S4 are having charge transfer (CT) type of excitation as per the HEI investigation. The SAR activity was examined using 5UFG protein, leading to the identification of two promising molecules.

Keywords

Fexinidazole Density functional theory Electrostatic potential Non-covalent interaction Structure activity relationship
Pushpam, E. J., & Jebaraj, J. W. (2024). DFT, Wave Function and SAR Analyses of Fexinidazole: A Drug for Sleeping Sickness. Asian Journal of Chemistry, 37(1), 75–92. https://doi.org/10.14233/ajchem.2025.32847
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. D. Malvy and F. Chappuis, Clin. Microbiol. Infect., 17, 986 (2011); https://doi.org/10.1111/j.1469-0691.2011.03536.x
  2. P.P. Simarro, A. Diarra, J.A. Ruiz Postigo, J.R. Franco and J.G. Jannin, PLoS Negl. Trop. Dis., 5, e1007 (2011); https://doi.org/10.1371/journal.pntd.0001007
  3. M. Balasegaram, S. Balasegaram, D. Malvy and P. Millet, PLoS Negl. Trop. Dis., 2, e234 (2008); https://doi.org/10.1371/journal.pntd.0000234
  4. F.A.S. Kuzoe, Acta Trop., 54, 153 (1993); https://doi.org/10.1016/0001-706X(93)90089-T
  5. D.H. Molyneux, Trans. R. Soc. Trop. Med. Hyg., 95, 233 (2001); https://doi.org/10.1016/S0035-9203(01)90220-2
  6. G. Hide, Clin. Microbiol. Rev., 12, 112 (1999); https://doi.org/10.1128/CMR.12.1.112
  7. F. Torrico, J. Gascón, L. Ortiz, J. Pinto, G. Rojas, A. Palacios, F. Barreira, B. Blum, A.G. Schijman, M. Vaillant, N. Strub-Wourgaft, M.J. Pinazo, G. Bilbe and I. Ribeiro, Clin. Infect. Dis., 76, e1186 (2023); https://doi.org/10.1093/cid/ciac579
  8. E.D. Deeks, Drugs, 79, 215 (2019); https://doi.org/10.1007/s40265-019-1051-6
  9. Fexinidazole: FDA-Approved Drugs, U.S. Food and Drug Administration. (Retrieved 16 July 2021).
  10. N. Kerru, L. Gummidi, S.V.H.S. Bhaskaruni, S.N. Maddila, P. Singh and S.B. Jonnalagadda, Sci. Rep., 9, 19280 (2019); https://doi.org/10.1038/s41598-019-55793-5
  11. N.D. Yilmazer and M. Korth, J. Phys. Chem. B, 117, 8075 (2013); https://doi.org/10.1021/jp402719k
  12. C. Faber, P. Boulanger, C. Attaccalite, I. Duchemin and X. Blase, Phil. Trans. R. Soc., A:, 372, 0271 (2013); https://doi.org/10.1098/rsta.2013.0271
  13. ACD/Chemsketch, 2017.2.1, Advanced Chemistry Development, Inc. (ACD/Labs), oronto, ON, Canada; www.acdlabs.com
  14. M.D. Hanwell, D.E. Curtis, D.C. Lonie, T. Vandermeersch, E. Zurek and G.R. Hutchison, J. Cheminform., 4, 17 (2012); https://doi.org/10.1186/1758-2946-4-17
  15. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Peterson, H. Nakatsuji, X. Li, M. Caricato, A.V. Marenich, J. Bloino, B.G. Janesko, R.Comperts, B. Mennucci, H.P. Hratchian, J.V.Oritz, A.F. Izmaylov, J.L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F.Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V.G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vereven, K. throssell, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro, M.J. Bearpark, J.J. Heyd, E.N. Borhters, K.N. Kudin, V.N. Staroverov, T.A. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A.P. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, J.M. Millam. M. Klene, C. Adamo, R. Cammi, J.W. Ochterski, R.L. Martin, K. Morokuma, O. Farkas, J.B. Forseman and D.J. Fox, Gaussian 16, Revision B.01, Gaussian, Inc., Wallingford CT (2016).
  16. R. Dennington, T.A. Keith and J.M. Millam, GaussView, Version 6, Semichem Inc., Shawnee Mission, K.S. (2016).
  17. A.D. Becke, J. Chem. Phys., 98, 5648 (1993); https://doi.org/10.1063/1.464913
  18. C. Lee, W.X. Yang and R.G. Parr, Phys. Rev. B Condens. Matter, 37, 785 (1988); https://doi.org/10.1103/PhysRevB.37.785
  19. N. Singla and P. Chowdhury, J. Mol. Struct., 1045, 72 (2013); https://doi.org/10.1016/j.molstruc.2013.04.015
  20. N.M. O’Boyle, A.L. Tenderholt and K.M. Langner, J. Comput. Chem., 29, 839 (2008); https://doi.org/10.1002/jcc.20823
  21. T. Lu and F. Chen, J. Comput. Chem., 33, 580 (2012); https://doi.org/10.1002/jcc.22885
  22. T. Lu and Q. Chen, Comput. Theor. Chem., 1200, 113249 (2021); https://doi.org/10.1016/j.comptc.2021.113249
  23. W. Humphrey, A. Dalke and K. Schulten, J. Mol. Graph., 14, 33 (1996); https://doi.org/10.1016/0263-7855(96)00018-5
  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. T. Sasitha and W.J. John, Heliyon, 7, e06127 (2021); https://doi.org/10.1016/j.heliyon.2021.e06127
  26. Y. Diao, W.Y. Wang, Z.H. Wei and J.L. Wang, Acta Crystallogr. Sect. E Struct. Rep. Online, 67, o3072 (2011); https://doi.org/10.1107/S1600536811041705
  27. A.I. Aranburu Leiva, S.L. Benjamin, S.K. Langley and R.E. Mewis, Acta Crystallogr. E Crystallogr. Commun., 72, 1614 (2016); https://doi.org/10.1107/S2056989016016753
  28. A. Schmidt, I. Jourdain, M. Knorr and C. Strohmann, Acta Crystallogr. E Crystallogr. Commun., 79, 516 (2023); https://doi.org/10.1107/S2056989023003717
  29. H. El-Ouafy, M. Aamor, M. Oubenali, M. Mbarki, A.E. Haimouti and T. El-Ouafy, Sci. Technol Asia, 27, 9 (2022).
  30. R. Rahmani, N. Boukabcha, A. Chouaih, F. Hamzaoui and S. Goumri-Said, J. Mol. Struct., 1155, 484 (2018); https://doi.org/10.1016/j.molstruc.2017.11.033
  31. S. Jeyavijayan, Spectrochim. Acta A Mol. Biomol. Spectrosc., 136, 890 (2015); https://doi.org/10.1016/j.saa.2014.09.110
  32. T.H.M. Nayaka, I. Pushpavathi, Pavithra and Y.R. Nagesh, Russ. J. Bioorg. Chem., 50, 211 (2024); https://doi.org/10.1134/S1068162024010229
  33. S. Saravanan and V. Balachandran, Spectrochim. Acta A Mol. Biomol. Spectrosc., 138, 406 (2015); https://doi.org/10.1016/j.saa.2014.11.091
  34. G. Kanimozhi, S. Tamilselvan, A. Saral, S. Kaleeswaran, E. Geetha, A. Manikandan and S. Muthu, Chem. Phys. Impact, 8, 100539 (2024); https://doi.org/10.1016/j.chphi.2024.100539
  35. M. Ragamathunnisa, M. Revathi and M.J.V. Rani, J. Adv. Appl. Sci. Res., 1, 1 (2015).
  36. R. Rajkumar, A. Kamaraj, S. Bharanidharan, H. Saleem and K. Krishnasamy, J. Mol. Struct., 1084, 74 (2015); https://doi.org/10.1016/j.molstruc.2014.10.035
  37. H. Moghanian, A. Mobinikhaledi and R. Monjezi, J. Mol. Struct., 1052, 135 (2013); https://doi.org/10.1016/j.molstruc.2013.08.043
  38. B. Rajasekhar, P.K. Muhammad Hijaz and T. Swu, J. Mol. Struct., 1168, 212 (2018); https://doi.org/10.1016/j.molstruc.2018.04.090
  39. L.T. Cheng, W. Tam, S.H. Stevenson, G.R. Meredith, G. Rikken and S.R. Marder, J. Phys. Chem., 95, 10631 (1991); https://doi.org/10.1021/j100179a026
  40. P. Kaatz, E.A. Donley and D.P. Shelton, J. Chem. Phys., 108, 849 (1998); https://doi.org/10.1063/1.475448
  41. C. Adant, M. Dupuis and J.L. Bredas, Int. J. Quantum Chem., 56(S29), 497 (1995); https://doi.org/10.1002/qua.560560853
  42. A. Sagaama, N. Issaoui, O. Al-Dossary, A.S. Kazachenko and M.J. Wojcik, J. King Saud Univ. Sci., 33, 101606 (2021); https://doi.org/10.1016/j.jksus.2021.101606
  43. Z. Jia, H. Pang, H. Li and X. Wang, Theor. Chem. Acc., 138, 113 (2019); https://doi.org/10.1007/s00214-019-2502-6
  44. S. Khan, H. Sajid, K. Ayub and T. Mahmood, J. Mol. Liq., 316, 113860 (2020); https://doi.org/10.1016/j.molliq.2020.113860
  45. M.L. Beatrice, S.M. Delphine, M. Amalanathan, M.S.M. Mary, H.M. Robert and K.T. Mol, J. Mol. Struct., 1238, 130381 (2021); https://doi.org/10.1016/j.molstruc.2021.130381
  46. R.R. Pillai, V.V. Menon, Y.S. Mary, S. Armakovic, S.J. Armakovic and C.Y. Panicker, J. Mol. Struct., 1130, 208 (2017); https://doi.org/10.1016/j.molstruc.2016.10.032
  47. P.K. Chattaraj, B. Maiti and U. Sarkar, J. Phys. Chem. A, 107, 4973 (2003); https://doi.org/10.1021/jp034707u
  48. C. Morell, A. Grand and A. Toro-Labbé, J. Phys. Chem. A, 109, 205 (2005); https://doi.org/10.1021/jp046577a
  49. C. James, A.A. Raj, R. Reghunathan, V.S. Jayakumar and I.H. Joe, J. Raman Spectrosc., 37, 1381 (2006); https://doi.org/10.1002/jrs.1554
  50. E.S. Ashlin, G.E. Sheela and P.R. Babila, Chem. Phys. Impact, 6, 100186 (2023); https://doi.org/10.1016/j.chphi.2023.100186
  51. R. Kumar, A. Kumar, V. Deval, A. Gupta, P. Tandon, P.S. Patil, P. Deshmukh, D. Chaturvedi and J.G. Watve, J. Mol. Struct., 1129, 292 (2017); https://doi.org/10.1016/j.molstruc.2016.09.087
  52. Z. Liu, T. Lu and Q. Chen, Carbon, 165, 461 (2020); https://doi.org/10.1016/j.carbon.2020.05.023
  53. J. Poater, M. Duran, M. Solà and B. Silvi, Chem. Rev., 105, 3911 (2005); https://doi.org/10.1021/cr030085x
  54. C.W. Bird, Tetrahedron, 41, 1409 (1985); https://doi.org/10.1016/S0040-4020(01)96543-3
  55. E. Matito, M. Duran and M. Solà, J. Chem. Phys., 122, 014109 (2005); https://doi.org/10.1063/1.1824895
  56. T.M. Krygowski, J. Chem. Inf. Comput. Sci., 33, 70 (1993); https://doi.org/10.1021/ci00011a011
  57. B. Donner, M. Kleber, C. Bracher and H.J. Kreuzer, Am. J. Phys., 73, 690 (2005); https://doi.org/10.1119/1.1930867
  58. H.L. Schmider and A.D. Becke, J. Mol. Struct. THEOCHEM, 527, 51 (2000); https://doi.org/10.1016/S0166-1280(00)00477-2
  59. M.R. Bozorgmehr, J. Chamani and G. Moslehi, J. Biomol. Struct. Dyn., 33, 1669 (2015); https://doi.org/10.1080/07391102.2014.967299
  60. O. Noureddine, N. Issaoui, M. Medimagh, O. Al-Dossary and H. Marouani, J. King Saud Univ. Sci., 33, 101334 (2021); https://doi.org/10.1016/j.jksus.2020.101334
  61. M. Bitew, T. Desalegn, T.B. Demissie, A. Belayneh, M. Endale and R. Eswaramoorthy, PLoS One, 16, e0260853 (2021); https://doi.org/10.1371/journal.pone.0260853
  62. N. Mani, S. Suresh, M. Govindammal, S. Kannan, E.I. Paulraj, D. Nicksonsebastin and M. Prasath, Chem. Phys. Impact, 7, 100254 (2023); https://doi.org/10.1016/j.chphi.2023.100254
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 0 Download : 0