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Photoisomerization of Sulindac and Ozagrel Hydrochloride by Vitamin B2 Catalyst Under Visible Light Irradiation

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Abstract

Purpose

Photoisomerization of the E/Z-alkene structures of drugs is a matter of concern as it could result in potency loss and adverse side effects. This study focused on light-induced isomerization of sulindac and ozagrel hydrochloride catalyzed by concomitant vitamin B2 under light-emitting diode (LED) or fluorescent light.

Methods

In the presence of 0.05/0.03 equivalents of vitamin B2/flavin adenine dinucleotide (FAD), sulindac or ozagrel hydrochloride was irradiated with LED light (405 nm) or fluorescent light. The photoisomerization in CD3OD and D2O was monitored by 1H NMR spectroscopy.

Results

Sulindac and ozagrel hydrochloride isomerized in the presence of a catalytic amount of vitamin B2 or FAD under irradiation of 405 nm LED light and fluorescent light. Irradiation with LED light was found to be more effective than fluorescent light irradiation. The rate of photoisomerization was affected by the solvent, and the reaction in CD3OD proceeded faster than in D2O. Furthermore, ozagrel hydrochloride was more prone to isomerization than sulindac.

Conclusion

The catalytic activity of vitamin B2 or FAD was demonstrated in the photoisomerization reaction of sulindac and ozagrel hydrochloride. Considering that the rate of photoisomerization in D2O is very slow, the possibility of the occurrence of photoisomerization during clinical use is low. However, this study suggests that the interfusion of vitamin B2 or FAD under excessive light exposure should be avoided as a caution during intravenous administration of sulindac or ozagrel hydrochloride.

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References

  1. Moore DE. Principles and practice of drug photodegradation studies. J Pharm Biomed Anal. 1987;5:441–53.

    Article  CAS  Google Scholar 

  2. Albini A, Fasani E. Drugs: photochemistry and photostability. In: Albini A, Fasamo E, editors. Photochemistry of drugs: an overview and practical problems. Cambridge: Royal Society of Chemistry; 1998. p. 1–73.

    Google Scholar 

  3. Beijersbergan van Henegouwen GMJ. Medicinal photochemistry: phototoxic and phototherapeutic aspects of drugs. Adv Drug Res. 1997;29:79–170.

    Article  Google Scholar 

  4. Nudelman NS, Cabrera CG. Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets. J Pharm Sci. 2002;91:1274–86.

    Article  CAS  Google Scholar 

  5. Andrisano V, Gotti R, Leoni A, Cavrini V. Photodegradation studies on atenolol by liquid chromatography. J Pharm Biomed Anal. 1999;21:851–7.

    Article  CAS  Google Scholar 

  6. Mohamed A, Salama A, Nasser WS, Uheida A. Photodegradation of ibuprofen, cetirizine, and naproxen by PAN-MWCNT/TiO2−NH2 nanofiber membrane under UV light irradiation. Environ Sci Eur. 2018;30:47.

    Article  Google Scholar 

  7. Li P, Ge P, Ping S, Lin W, Zhang X, Wei C, et al. Photodegradation mechanism and influencing factors of asthma drug salmeterol under UV irradiation. J Photochem Photobiol A. 2021;404:112914.

    Article  Google Scholar 

  8. Maquille A, Salembier S, Hérent M-F, Jiwan J-LH. Photodegradation of flupentixol in aqueous solution under irradiation at 254 nm: identification of the photoproducts generated. J Photochem Phtobiol Chem. 2010;214:224–9.

    Article  CAS  Google Scholar 

  9. Wilson S, Ruenitz PC. Structural characterization and biological effects of photocyclized products of tamoxifen irradiation. J Pharm Sci. 1993;82:571–4.

    Article  CAS  Google Scholar 

  10. Dall’Acqua S, Vedaldi D, Salvador A. Isolation and structure elucidation of the main UV-A photoproducts of vandetanib. J Pharm Biomed Anal. 2013;84:196–200.

    Article  Google Scholar 

  11. Tashtoush BM, Jacobson EL, Jacobson MK. UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: implications for development of improved pharmaceutical formulations. Int J Pharm. 2008;352:123–8.

    Article  CAS  Google Scholar 

  12. Utsuki T, Imamura K, Hirayama F, Uekama K. Stoichiometry-dependent changes of solubility and photoreactivity of an antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes. Eur J Pharm Sci. 1993;1:81–7.

    Article  CAS  Google Scholar 

  13. Kumar N, Windisch V, Ammon HL. Photoinstability of some tryphostin drugs: chemical consequences of crystallinity. Pharm Res. 1995;12:1708–15.

    Article  CAS  Google Scholar 

  14. Metternich JB, Gilmour R. A bio-inspired, catalytic E → Z isomerization of activated olefins. J Am Chem Soc. 2015;137:11254–7.

    Article  CAS  Google Scholar 

  15. Drugs@FDA: FDA-Approved Drugs: https://www.accdssdata.fda.gov/scripts/cder/daf/. accessed Feb. 2

  16. Kawabata K, Akimoto S, Nishi H. Cis–trans isomerization reaction of sulindac induced by UV Irradiation in the aqueous media. Chromatography. 2018;39:139–46.

    Article  CAS  Google Scholar 

  17. Shuman RF, Pines SH, Shearin WE, Czaja RF, Abramson NL, Tull R. A sterically efficient synthesis of (Z)-5-fluoro-2-methyl-l-(p-methylthiobenzylidene)-3-indenylacetic acid and its S-oxide, sulindac. J Org Chem. 1977;42:1914–9.

    Article  CAS  Google Scholar 

  18. Olpp T, Brückner R. Stereoselective preparation of (E)-a-bromo acrylates from mixtures of brominated Ando phosphonates. Synthesis. 2004:2135–2152.

  19. Ugolnikov O, Ivanov S, Rannoux C, Salit A-F, Gander S, Thuilliez A-L. 1,3-Dipolar compound bearing an imidazole function. Ala; 2015. p. WO2015059269.A1 2015-04-30

  20. Yamada YM, Yuyama Y, Sato T, Fujikawa S, Uozumi Y. A palladium-nanoparticle and silicon-nanowire-array hybrid: a platform for catalytic heterogeneous reactions. Angew Chem. 2014;126:131–5.

    Article  Google Scholar 

  21. Peng J, Li F, Liang S, Huang Q. Preparation of cis-ozagrel. 2019. CN 110028454 A. 2019-07-19

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors declare that they have no conflicts of interest.

Funding

This work was supported in part by a Grant-in-Aid for Young Scientists (19K16454) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-shi, Chiba, 278-8510, Japan

    Mayuko Suga, Kosho Makino & Hideyo Takahashi

  2. Department of Medicinal Chemistry, Faculty of Pharma Sciences, Teikyo University, Itabashi-ku, Tokyo, Japan

    Hidetsugu Tabata & Tetsuta Oshitari

  3. Department of Medicinal Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    Hideaki Natsugari

Authors
  1. Mayuko Suga
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  2. Kosho Makino
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  3. Hidetsugu Tabata
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  4. Tetsuta Oshitari
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  5. Hideaki Natsugari
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  6. Hideyo Takahashi
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Contributions

Mayuko Suga, Kosho Makino, and Hideyo Takahashi contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Mayuko Suga, Kosho Makino, Hidetsugu Tabata, Tetsuta Oshitari, Natsugari Hideaki, and Hideyo Takahashi. The first draft of the manuscript was written by Mayuko Suga, Kosho Makino, and Hideyo Takahashi. All authors read and approved the final manuscript.

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Correspondence to Hideyo Takahashi.

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Suga, M., Makino, K., Tabata, H. et al. Photoisomerization of Sulindac and Ozagrel Hydrochloride by Vitamin B2 Catalyst Under Visible Light Irradiation. Pharm Res 39, 577–586 (2022). https://doi.org/10.1007/s11095-022-03203-3

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  • DOI: https://doi.org/10.1007/s11095-022-03203-3

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