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Experimental spectroscopic and molecular docking investigations of the anticancer drugs aprepitant and capecitabine

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Abstract

Cancer is one of the disorders that causes the most fatalities in modern times and is responsible for a significant number of deaths each year. The accurate administration of this disease has been hampered by a variety of factors including variances in the disease found in various regions of the globe. Several medications, in addition to diagnostic procedures, have evolved as a result of advancements in scientific research in order to treat certain cancers and have contributed to the cure of this disease to some degree. The study of the medical repercussions of cancer remains an intriguing and important subject of interest even after all the efforts that have been accomplished over a long period of scientific research. The purpose of this work was to contribute to the advancement of such fundamental scientific research by describing the attribution of unique modes of vibration of the antiemetic aprepitant as well as the anticancer medication capecitabine. Using standard FT-IR spectrum analysis and molecular docking techniques, the exact atomic-level mechanism of aprepitant and capecitabine is determined, by targeting the human NK1 substance P receptor (Human brain NK1 receptor) and thymidine phosphatase (cancer tissue) proteins. The quantum mechanical wavelength–energy relation was used to anticipate the associated energy intervals in order to assess the bioactivity of the molecules and the transfer of charge between HOMO and LUMO orbitals. Molecular docking investigations of aprepitant and capecitabine with the NK1 receptor and the thymidine phosphorylase proteins have been determined, respectively. The root mean square deviation and binding energy, as well as the types of bonds formed and the exact pathway taken by the anticancer medications in their interaction with the receptor, are established. This knowledge may be used to improve the mechanism of action, efficacy, and effectiveness of NK1 receptor antagonist drugs and anticancer medication, as well as to design innovative anticancer agents.

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References

  1. Sung H et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/CAAC.21660

    Article  PubMed  Google Scholar 

  2. “Worldwide cancer statistics | Cancer research UK.” https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer#heading-Zero (Accessed Jan. 06, 2023)

  3. Stocks M (2013) The small molecule drug discovery process – from target selection to candidate selection. Introd Biol Small Mol Drug Res Dev Theory Case Stud. https://doi.org/10.1016/B978-0-12-397176-0.00003-0

    Article  Google Scholar 

  4. “Aprepitant.” Meyler’s Side Eff. Drugs 2016, https://doi.org/10.1016/B978-0-444-53717-1.00022-6

  5. Ruby C (2013) Aprepitant. xPharm Compr Pharmacol Ref. https://doi.org/10.1016/B978-008055232-3.63742-0

    Article  Google Scholar 

  6. House L, Ramirez J, Seminerio M, Mirkov S, Ratain MJ (2015) In vitro glucuronidation of aprepitant: a moderate inhibitor of UGT2B7. Xenobiotica 45(11):990–998. https://doi.org/10.3109/00498254.2015.1038743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ruby C (2010) Aprepitant. xPharm Compr Pharmacol Ref. https://doi.org/10.1016/B978-008055232-3.63742-0

    Article  Google Scholar 

  8. Jordan K, Feyer PC, Ortner P (2011) Prophylaxis and treatment of chemotherapy-induced nausea and vomiting. Support Oncol. https://doi.org/10.1016/B978-1-4377-1015-1.00003-5

    Article  Google Scholar 

  9. Wu YJ (2012) Heterocycles and medicine: a survey of the heterocyclic drugs approved by the U.S. FDA from 2000 to present. Prog Heterocycl Chem 24:1–53. https://doi.org/10.1016/B978-0-08-096807-0.00001-4

    Article  CAS  Google Scholar 

  10. Rider BJ (2007) Capecitabine. xPharm Compr Pharmacol Ref. https://doi.org/10.1016/B978-008055232-3.62967-8

    Article  Google Scholar 

  11. Janney LM, Waterbury NV (2005) Capecitabine-warfarin interaction. Ann Pharmacother 39(9):1546–1551. https://doi.org/10.1345/APH.1G153

    Article  PubMed  Google Scholar 

  12. “Melphalan | 148–82–3.” https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2492687.htm (Accessed Oct. 25, 2021)

  13. K R Cousins (2011)“Computer review of chemdraw ultra 120”. J Am Chem Soc 133(21): 8388 https://doi.org/10.1021/JA204075S

  14. Simmons MA (2010) Tachykinin receptor agents. xPharm Compr Pharmacol Ref. https://doi.org/10.1016/B978-008055232-3.63832-2

    Article  Google Scholar 

  15. Welston K, May D (2017) Gastrointestinal drugs. Side Eff Drugs Annu 39:373–387. https://doi.org/10.1016/BS.SEDA.2017.06.022

    Article  Google Scholar 

  16. Mader MM, Henry JR (2007) Antimetabolites. Compr Med Chem II:55–79. https://doi.org/10.1016/B0-08-045044-X/00204-2

    Article  Google Scholar 

  17. McMillin GA, Wadelius M, Pratt VM (2018) Pharmacogenetics. Princ Appl Mol Diagnostics. https://doi.org/10.1016/B978-0-12-816061-9.00011-4

    Article  Google Scholar 

  18. Wyatt MD, Wilson DM (2009) Participation of DNA repair in the response to 5-fluorouracil. Cell Mol Life Sci 66(5):788–799. https://doi.org/10.1007/S00018-008-8557-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. “UV/Vis/NIR Spectrophotometers and accessories | PerkinElmer.” https://www.perkinelmer.com/uk/category/uv-vis-spectroscopy-uv (Accessed Oct. 25, 2021)

  20. “IR spectrum table.” https://www.sigmaaldrich.com/IN/en/technical-documents/technical-article/analytical-chemistry/photometry-and-reflectometry/ir-spectrum-table (Accessed Oct. 25, 2021)

  21. “IR table.” https://www.chem.ucla.edu/~bacher/General/30BL/IR/ir.html (Accessed Oct. 25, 2021)

  22. Ramana PV et al (2022) Spectroscopic, quantum mechanical, electronic excitation properties (Ethanol solvent), DFT investigations and molecular docking analysis of an anti-cancer drug Bendamustine. J Mol Struct 1253:132211. https://doi.org/10.1016/j.molstruc.2021.132211

    Article  CAS  Google Scholar 

  23. Mariappan G, Sundaraganesan N, Manoharan S (2012) The spectroscopic properties of anticancer drug Apigenin investigated by using DFT calculations, FT-IR, FT-Raman and NMR analysis. Spectrochim Acta Part A Mol Biomol Spectrosc 1(95):86–99. https://doi.org/10.1016/j.saa.2012.04.089

    Article  CAS  Google Scholar 

  24. “Infrared spectra: identifying functional groups.” https://sites.science.oregonstate.edu/~gablek/CH335/Chapter10/IR.htm (Accessed Oct. 25, 2021)

  25. Joseph L, Sajan D, Chaitanya K, Devarajegowda HC, Isac J (2013) Density functional theory study, FT-iR and FT-Raman spectra and SQM force field calculation for vibrational analysis of 1, 3-Bis (hydroxymethyl) benzimidazolin-2-one. Spectrochim Acta Part A Mol Biomol Spectrosc 1(114):432–440. https://doi.org/10.1016/j.saa.2013.05.003

    Article  CAS  Google Scholar 

  26. Nagib DA, Macmillan DWC (2011) Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis. Nature 480(7376):224–228. https://doi.org/10.1038/nature10647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mary YS, Panicker CY, Anto PL, Sapnakumari M, Narayana B, Sarojini BK (2015) Molecular structure, FT-IR, NBO, HOMO and LUMO, MEP and first order hyperpolarizability of (2E)-1-(2, 4-dichlorophenyl)-3-(3, 4, 5-trimethoxyphenyl) prop-2-en-1-one by HF and density functional methods. Spectrochim Acta Part A Mol Biomol Spectrosc 25(135):81–92. https://doi.org/10.1016/J.SAA.2014.06.140

    Article  Google Scholar 

  28. Sertbakan TR (2017) Structure, spectroscopic and quantum chemical investigations of 4-Amino-2-Methyl-8-(Trifluoromethyl)quinoline. Celal Bayar Üniv Fen Bilim Derg 13(4):851–861. https://doi.org/10.18466/cbayarfbe.339858

    Article  CAS  Google Scholar 

  29. Sri NU, Chaitanya K, Prasad MV, Veeraiah V, Veeraiah A (2012) Experimental (FT-IR, FT-Raman and UV–Vis spectra) and density functional theory calculations of diethyl 1H-pyrazole-3, 5-dicarboxylate. J Mol Struct 18(1019):68–79. https://doi.org/10.1016/j.molstruc.2012.03.032

    Article  CAS  Google Scholar 

  30. Compounds O (1964) CS stretching frequency. Science 42(80):36–42

    Google Scholar 

  31. Prasad KV, Muthu S, Santhamma C (2017) Spectroscopic (FT-IR, FT-Raman, UV–Visible) and quantum chemical studies of 4-Chloro-3-iodobenzophenone. J Mol Struct 15(1128):685–693. https://doi.org/10.1016/J.MOLSTRUC.2016.09.037

    Article  Google Scholar 

  32. Liu J et al (2015) Characterization and pharmacokinetic study of aprepitant solid dispersions with soluplus®. Molecules 20(6):11345–11356. https://doi.org/10.3390/molecules200611345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Helmy R et al (2003) Characterization and quantitation of aprepitant drug substance polymorphs by attenuated total reflectance Fourier transform infrared spectroscopy. Anal Chem 75(3):605–611. https://doi.org/10.1021/ac020538i

    Article  PubMed  Google Scholar 

  34. Atkins M, López IG, Kuo B (2022) Nausea and vomiting. Compr Pharmacol. https://doi.org/10.1016/B978-0-12-820472-6.00182-1

    Article  Google Scholar 

  35. Prasad KV, Samatha K, Rao DJ, Santhamma C, Muthu S, Heron BM (2015) Spectroscopic studies (FT-IR, FT-Raman, UV–Visible), normal co-ordinate analysis, first-order hyperpolarizability and HOMO, LUMO studies of 3, 4-dichlorobenzophenone by using density functional methods. Spectrochim Acta Part A Mol Biomol Spectrosc 5(151):644–654. https://doi.org/10.1016/j.saa.2015.07.001

    Article  CAS  Google Scholar 

  36. Mary YS, Jojo PJ, Panicker CY, Van Alsenoy C, Ataei S, Yildiz I (2014) “Theoretical investigations on the molecular structure, vibrational spectra, HOMO–LUMO and NBO analysis of 5-chloro-2-((4-chlorophenoxy)methyl)benzimidazole.” Spectrochim Acta Part A Mol Biomol Spectrosc 122:499–511. https://doi.org/10.1016/J.SAA.2013.11.025

    Article  CAS  Google Scholar 

  37. Mary YS, Jojo PJ, Panicker CY, Van Alsenoy C, Ataei S, Yildiz I (2014) Quantum mechanical and spectroscopic (FT-IR, FT-Raman, 1H NMR and UV) investigations of 2-(phenoxy methyl)benzimidazole. Spectrochim Acta Part A Mol Biomol Spectrosc. https://doi.org/10.1016/J.SAA.2014.01.068

    Article  Google Scholar 

  38. “Aprepitant,” Meyler’s Side Eff Drugs, p 657, 2016, https://doi.org/10.1016/B978-0-444-53717-1.00022-6

  39. “Aprepitant: uses, interactions, mechanism of action | drugbank online.” https://go.drugbank.com/drugs/DB00673 (Accessed Jun. 18, 2022)

  40. Dolan RD, Rohani TS, Muttineni D, Mashimo H (2022) The physiology and pharmacology of diabetic gastropathy management. Compr Pharmacol. https://doi.org/10.1016/B978-0-12-820472-6.00045-1

    Article  Google Scholar 

  41. Prasad KV, Ramana PV (2023) Vibrational spectroscopic studies, DFT, and molecular docking investigations of 4-fluoro-3-methyl benzophenone. Vib Spectrosc 1(126):103532. https://doi.org/10.1016/j.vibspec.2023.103532

    Article  CAS  Google Scholar 

  42. Beauchamp spectroscopy tables 1. https://edisciplinas.usp.br/pluginfile.php/6971133/mod_resource/content/1/spec_ir_nmr_spectra_tables.pdf

  43. Alen S, Sajan D, Joseph L, Chaitanya K, Shettigar V, Jothy VB (2015) Synthesis, growth, vibrational spectral investigations and structure-property relationship of an organic NLO crystal: 3,4-dimethoxy chalcone. Chem Phys Lett 636:208–215. https://doi.org/10.1016/j.cplett.2015.07.030

    Article  CAS  Google Scholar 

  44. Ramana PV, Krishna YR, Mouli KC (2022) Experimental FT-IR and UV–Vis spectroscopic studies and molecular docking analysis of anti-cancer drugs exemestane and Pazopanib. J Mol Struct 5(1263):133051. https://doi.org/10.1016/j.molstruc.2022.133051

    Article  CAS  Google Scholar 

  45. Yahyaei B, Pourali P (2019) One step conjugation of some chemotherapeutic drugs to the biologically produced gold nanoparticles and assessment of their anticancer effects. Sci Rep 9(1):1–16. https://doi.org/10.1038/s41598-019-46602-0

    Article  CAS  Google Scholar 

  46. Martino R, Gilard V, Malet-Martino M (2008) Fluorine-19 or Phosphorus-31 NMR spectroscopy: a powerful technique for biofluid metabolic studies and pharmaceutical formulation analysis of fluorinated or phosphorylated drugs. NMR Spectrosc Pharm Anal. https://doi.org/10.1016/B978-0-444-53173-5.00015-9

    Article  Google Scholar 

  47. Vardanyan R, Hruby V (2016) Antineoplastic agents. Synth Best-Seller Drugs. https://doi.org/10.1016/B978-0-12-411492-0.00028-6

    Article  Google Scholar 

  48. “Antineoplastic agents”. Cancer Bull 27(5): 80–82, 1975, https://doi.org/10.1016/B978-0-12-411492-0.00028-6

  49. Reddy VP (2015) Organofluorine compounds as anticancer agents. Organofluor Compd Biol Med. https://doi.org/10.1016/B978-0-444-53748-5.00009-5

    Article  Google Scholar 

  50. Shrivastava N, Iqbal B, Ali J, Baboota S (2021) Chemopreventive and therapeutic potential of natural agents and their combinations for breast cancer. Discov Dev Anti-Breast Cancer Agents from Nat Prod. https://doi.org/10.1016/B978-0-12-821277-6.00009-X

    Article  Google Scholar 

  51. “Everolimus: uses, interactions, mechanism of action | drugbank online.” https://go.drugbank.com/drugs/DB01590 (Accessed Oct. 25, 2021)

  52. Balaev VV, Prokofev II, Gabdoulkhakov AG, Betzel C, Lashkov AA (2018) Crystal structure of pyrimidine-nucleoside phosphorylase from Bacillus subtilis in complex with imidazole and sulfate. Acta Crystallogr Sect F: Struct Biol Commun 74(4):193–197. https://doi.org/10.1107/S2053230X18002935

    Article  CAS  Google Scholar 

  53. Adeniji SE, Uba S, Uzairu A (2019) Molecular docking study for evaluating the binding mode and interaction of 2, 4-disubstituted quinoline and its derivatives as potent anti-tubercular agents against Lipoate protein B (LipB). Turk Comput Theor Chem 3(1):17–24. https://doi.org/10.33435/tcandtc.458615

    Article  CAS  Google Scholar 

  54. Jones D et al (2021) Improved protein-ligand binding affinity prediction with structure-based deep fusion inference. J Chem Inf Model 61(4):1583–1592. https://doi.org/10.1021/acs.jcim.0c01306

    Article  CAS  PubMed  Google Scholar 

  55. Gurung AB, Bhattacharjee A, Ali MA (2016) Exploring the physicochemical profile and the binding patterns of selected novel anticancer Himalayan plant-derived active compounds with macromolecular targets. Inform Med Unlocked 5(July):1–14. https://doi.org/10.1016/j.imu.2016.09.004

    Article  Google Scholar 

  56. Raajaraman BR, Sheela NR, Muthu S (2019) Spectroscopic, quantum computational and molecular docking studies on 1-phenylcyclopentane carboxylic acid. Comput Biol Chem 82:44–56. https://doi.org/10.1016/J.COMPBIOLCHEM.2019.05.011

    Article  CAS  PubMed  Google Scholar 

  57. Lawley PD, Phillips DH (1996) DNA adducts from chemotherapeutic agents. Mutat Res—Fundam Mol Mech Mutagen 355(1–2):13–40. https://doi.org/10.1016/0027-5107(96)00020-6

    Article  Google Scholar 

  58. Povirk LF, Shuker DE (1994) DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res Genet Toxicol 318(3):205–226. https://doi.org/10.1016/0165-1110(94)90015-9

    Article  CAS  Google Scholar 

  59. “RCSB PDB - 4X46: X-RAY structure thymidine phosphorylase from Salmonella typhimurium complex with SO4 at 2.19 A.” https://www.rcsb.org/structure/4X46 (Accessed Jun. 18, 2022)

  60. Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2):455–461. https://doi.org/10.1002/JCC.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. “Free download: BIOVIA discovery studio visualizer - dassault systèmes.” https://discover.3ds.com/discovery-studio-visualizer-download (Accessed Sep. 06, 2021)

  62. Ramana PV, Krishna YR, Mouli KC (2022) Experimental ( FT-IR, UV-Vis ) spectroscopic analysis and molecular docking investigations of anti-cancer drugs Alkeran and Bicalutamide. J Mol Struct 1270:133984. https://doi.org/10.1016/j.molstruc.2022.133984

    Article  CAS  Google Scholar 

  63. Malińska M et al (2014) Crystal structure and tautomerism of capecitabine. J Pharm Sci 103(2):587–593. https://doi.org/10.1002/jps.23831

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Engineering Physics, A.U. College of Engineering (A), Andhra University, Visakhapatnam, 530003, India

    P. Venkata Ramana

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P. VR contributed to the conceptualization, methodology, investigation, validation, software, formal analysis, writing—original draft, writing—editing, visualization, supervision, project administration and resources.

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Correspondence to P. Venkata Ramana.

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Ramana, P.V. Experimental spectroscopic and molecular docking investigations of the anticancer drugs aprepitant and capecitabine. Theor Chem Acc 142, 114 (2023). https://doi.org/10.1007/s00214-023-03055-z

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