Photochemical Е/Z isomerization of isonicotinoyl hydrazones based on pyridoxine derivatives
https://doi.org/10.26907/2542-064X.2025.2.254-267
Abstract
Isonicotinoyl hydrazone of 6-carbaldehyde pyridoxine 1, existing as a mixture of E and Z isomers, is known to exhibit potent activity against drug-resistant strains of M. tuberculosis. This article continues earlier research on the development of anti-tuberculosis drugs by examining the photostability of compound 1 and its structural analogs, which is important for the production of pharmaceutical substances and the determination of the specific activity of various isomers in vivo. Under the action of UV irradiation, a significant tarring of the reaction mixture in the solutions of compounds 1 and 2 containing free hydroxymethyl groups at positions 4 and 5 of pyridoxine was observed, apparently due to the formation of reactive ortho-quinone methides. However, when ketal protection was employed for hydroxymethyl groups in the pyridoxine derivative containing the isonicotinoyl hydrazone fragment at position 6, a transition from the thermodynamically more stable E isomer to Z isomer was induced by UV irradiation through the formation of an intramolecular hydrogen bond of the NH...Npyr type. In contrast, owing to the presence of an intramolecular hydrogen bond of the OH...NC=N type, the pyridoxine derivative bearing the isonicotinoyl hydrazone fragment at position 2, underwent no significant photoisomerization.
Supporting agencies: This study was funded by the subsidy allocated to Kazan Federal University for the project part of the state assignment in the sphere of scientific activities (project no. FZSM-2023-0010)
About the Authors
N. V. Shtyrlin
Kazan Federal University
Russian Federation
Competing Interests:
Russian Federation
Nikita V. Shtyrlin - Cand. Sci. (Chemistry), Senior Researcher, Scientific and Educational Center for Pharmacy.
Kazan
Competing Interests:
The authors declare no conflicts of interest
R. M. Khaziev
Kazan Federal University
Russian Federation
Competing Interests:
Russian Federation
Rail M. Khaziev - Cand. Sci. (Chemistry), Researcher, Scientific and Educational Center for Pharmacy.
Kazan
Competing Interests:
The authors declare no conflicts of interest
D. R. Islamov
FRC Kazan Scientific Center, Russian Academy of Sciences
Russian Federation
Competing Interests:
Russian Federation
Daut R. Islamov - Cand. Sci. (Chemistry), Senior Researcher, Laboratory for Structural Analysis of Biomacromolecules.
Kazan
Competing Interests:
The authors declare no conflicts of interest
Y. G. Shtyrlin
Kazan Federal University
Russian Federation
Competing Interests:
Russian Federation
Yurii G. Shtyrlin - Dr. Sci. (Chemistry), Associate Professor, Leading Researcher, Scientific and Educational Center for Pharmacy.
Kazan
Competing Interests:
The authors declare no conflicts of interest
References
1. Socea L.-I., Barbuceanu S.-F., Pahontu E.M., Dumitru A.-C., Nitulescu G.M., Sfetea R.C., Apostol T.-V. Acylhydrazones and their biological activity: A review. Molecules, 2022, vol. 27, no. 24, art. 8719. https://doi.org/10.3390/molecules27248719.
2. Jabeen M. A comprehensive review on analytical applications of hydrazone derivatives. J. Turk. Chem. Soc., Sect. A, 2022, vol. 9, no. 3, pp. 663–698. https://doi.org/10.18596/jotcsa.1020357.
3. Lv Y., Meng J., Li C., Wang X., Ye Y., Sun K. Update on the synthesis of N-heterocycles via cyclization of hydrazones (2017–2021). Adv. Synth. Catal., 2021, vol. 363, no. 23, pp. 5235–5265. https://doi.org/10.1002/adsc.202101184.
4. Shao B., Aprahamian I. Hydrazones as new molecular tools. Chem, 2020, vol. 6, no. 9, pp. 2162–2173. https://doi.org/10.1016/j.chempr.2020.08.007.
5. Su X., Aprahamian I. Hydrazone-based switches, metallo-assemblies and sensors. Chem. Soc. Rev., 2014, vol. 43, no. 6, pp. 1963–1981. https://doi.org/10.1039/C3CS60385G.
6. Palla G., Predieri G., Domiano P., Vignali C., Turner W. Conformational behaviour and E/Z isomerization of N-acyl and N-aroylhydrazones. Tetrahedron, 1986, vol. 42, no. 13, pp. 3649–3654. https://doi.org/10.1016/S0040-4020(01)87332-4.
7. Shchukina M.N., Pershin G.N., Sazonova E.D., Makeeva O.O. Aromatic isonicotinoyl hydrazones, a new class of chemotherapeutic anti-tuberculosis substances. Probl. Tuberk., 1954, no. 2, pp. 44–50. (In Russian)
8. Ridahunlang N., Bisht R., Rishanlang N. Isoniazid derivatives as anti-tubercular agents: From structural design to clinical investigations. Infect. Disord.: Drug Targets, 2023, vol. 23, no. 3, pp. 44–68. https://doi.org/10.2174/1871526522666221004152324.
9. Hu Y.-Q., Zhang S., Zhao F., Gao C., Feng L.-S., Lv Z.-S., Xu Z., Wu X. Isoniazid derivatives and their anti-tubercular activity. Eur. J. Med. Chem., 2017, vol. 133, pp. 255–267. https://doi.org/10.1016/j.ejmech.2017.04.002.
10. Sah P.P.T. Nicotinyl and isonicotinyl hydrazones of pyridoxal. J. Am. Chem. Soc., 1954, vol. 76, no. 1, p. 300. https://doi.org/10.1021/ja01630a096.
11. Poñka P., Borová J., Neuwirt J., Fuchs O. Mobilization of iron from reticulocytes: Identification of pyridoxal isonicotinoyl hydrazone as a new iron chelating agent. FEBS Lett., 1979, vol. 97, no. 2, pp. 317–321. https://doi.org/10.1016/0014-5793(79)80111-8.
12. Lim C.K., Kalinowski D.S., Richardson D.R. Protection against hydrogen peroxide-mediated cytotoxicity in Friedreich’s ataxia fibroblasts using novel iron chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone class. Mol. Pharmacol., 2008, vol. 74, no. 1, pp. 225–235. https://doi.org/10.1124/mol.108.046847.
13. Singh Y.P., Pandey A., Vishwakarma S., Modi G. A review on iron chelators as potential therapeutic agents for the treatment of Alzheimer’s and Parkinson’s diseases. Mol. Diversity, 2019, vol. 23, no. 2, pp. 509–526. https://doi.org/10.1007/s11030-018-9878-4.
14. Shtyrlin N.V., Khaziev R.M., Shtyrlin V.G., Gilyazetdinov E.M., Agafonova M.N., Usachev K.S., Islamov D.R., Klimovitskii A.E., Vinogradova T.I., Dogonadze M.Z., Zabolotnykh N.V., Sokolovich E.G., Yablonskiy P.K., Shtyrlin Y.G. Isonicotinoyl hydrazones of pyridoxine derivatives: Synthesis and antimycobacterial activity. Med. Chem. Res., 2021, vol. 30, no. 4, pp. 952–963. https://doi.org/10.1007/s00044-021-02705-w.
15. Bartolić M, Matošević A, Maraković N, Bušić V, Roca S, Vikić-Topić D, Sabljić A, Bosak A, Gašo-Sokač D. Evaluation of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2024, vol. 39, no. 1, art. 2431832. https://doi.org/10.1080/14756366.2024.2431832.
16. GPM.1.1.0029. Photostability testing of medicinal products. State Pharmacopoeia of the Russian Federation. XV ed. Vol. 1. Moscow, Minist. Zdravookhr. Ross. Fed., 2023, pp. 412–421. (In Russian)
17. Sheldrick G.M. SHELXT – integrated space-group and crystal-structure determination. Acta Crystallogr., Sect. A, 2015, vol. 71, pt. 1, pp. 3–8. https://doi.org/10.1107/S2053273314026370.
18. Sheldrick G.M. A short history of SHELX. Acta Crystallogr., Sect. A., 2007, vol. 64, pt. 1, pp. 112–122. https://doi.org/10.1107/S0108767307043930.
19. Macrae C.F., Edgington P.R., McCabe P., Pidcock E., Shields G.P., Taylor R., Towler M., Van De Streek J. Visualization and analysis of crystal structures. J. Appl. Crystallogr., 2006, vol. 39, pp. 453–457. https://doi.org/10.1107/S002188980600731X.
20. Brousmiche D.W., Wan P. Photogeneration of quinone methide-type intermediates from pyridoxine and derivatives. J. Photochem. Photobiol. A., 2002, vol. 149, nos. 1–3, pp. 71–81. https://doi.org/10.1016/S1010-6030(01)00654-2.
21. Shtyrlin N.V., Lodochnikova O.A., Shtyrlin Y.G. Regioisomeric oximes and thiosemicarbazones derived from 6-substituted pyridoxines. Mendeleev Commun., 2012, vol. 22, no. 3, pp. 169–170. https://doi.org/10.1016/j.mencom.2012.05.021.
22. Aarjane M., Slassi S., Amine A. Novel series of N-acylhydrazone based on acridone: Synthesis, conformational and theoretical studies. J. Mol. Struct., 2021, vol. 1225, art. 129079. https://doi.org/10.1016/j.molstruc.2020.129079.
23. Syakaev V.V., Podyachev S.N., Buzykin B.I., Latypov S.K., Habicher W.D., Konovalov A.I. NMR study of conformation and isomerization of aryland heteroarylaldehyde 4-tert-butylphenoxyacetylhydrazones. J. Mol. Struct., 2006, vol. 788, nos. 1–3, pp. 55–62. https://doi.org/10.1016/j.molstruc.2005.11.018.
24. Agrawal K.C., Clayman S., Sartorelli A.C. Synthesis of site-directed chelating agents II: 2-Formyl3-hydroxy-4,5-bis (hydroxymethyl) pyridine thiosemicarbazone. J. Pharm. Sci., 1976, vol. 65, no. 2, pp. 297–300. https://doi.org/10.1002/jps.2600650231.
Review
For citations:
Shtyrlin N.V., Khaziev R.M., Islamov D.R., Shtyrlin Y.G. Photochemical Е/Z isomerization of isonicotinoyl hydrazones based on pyridoxine derivatives. Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki. 2025;167(2):254-267. (In Russ.) https://doi.org/10.26907/2542-064X.2025.2.254-267
Views:
59
Email this article 