LEUCINE ETHYL ESTER REACTIVITY IN BENZOYLATION IN WATER-ORGANIC MEDIA
Abstract
On a base of experimental study of the kinetics of D,L-leucine ethyl ester interaction with 2,4-dinitrophenyl and 2,4,6-trinitrophenyl esters of benzoic acid in four binary water-organic solvents in the temperature interval 298–318 К, the range of rate constants change k298 = 0.011-1.45 l·mole-1·s-1 was established and the reactions activation barriers were determined: ΔH≠298 = 19-69 kJ·mol-1; -ΔS≠298 = 22-165 J·mol-1·K-1. It has been established that leucine ethyl ester is much less reactive in benzoylation than the free amino acids. The effect of nature and composition of the solvents containing ethanol, isopropanol, acetonitrile, and 1,4-dioxane as a non-aqueous component on the reaction rate has been studied. It is shown that with an increase in water proportion in the binary solvent from 20 to 80 wt.%, the rate constants of all the studied reactions increase significantly. Comparison of the processes kinetic characteristics made it possible to choose water-alcohol systems as the most preferable for the leucine ethyl ester benzoylation. In all reaction series, a compensatory effect on the composition of the solvent was found. The values of isokinetic temperatures are in the range typical for nucleophilic substitution reactions on the carbonyl reaction center. The results of virtual screening of the biological activity of D,L-leucine ethyl ester and its benzoylation product indicate that these objects exhibit high inhibitory activity against hydrolase enzymes that belong to the peptidase subclass. At the same time, the inhibitory effect of the leucine ethyl ester benzoylation product on oxidoreductases is noticeably reduced compared to leucine. Leucine modification at the N- and C-terminal groups leads to a significant decrease in the compounds toxicity, which indicates the prospects for further study of Bz-NH- and COOEt-derivatives of leucine.
For citation:
Kustova T.P., Kochetova L.B. Leucine ethyl ester reactivity in benzoylation in water-organic media. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 12. P. 41-48. DOI: 10.6060/ivkkt.20236612.6892.
References
Sargsyan H.R., Grigoryan G.S., Markarian S.A. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 2. P. 62-69. DOI: 10.6060/ ivkkt.20236602.6740.
Tyunina E.Yu., Kuritsyna A.A. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2019. V. 62. N 11. P. 78-84. DOI: 10.6060/ivkkt.20196211.6082.
Ksenofontova K. V., Ksenofontov A. A., Khodov I. A., Rumyantsev E. V. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2020. V. 63. N 5. P. 4-11. DOI: 10.6060/ivkkt.20206305.6101.
Makarov S.V., Pokrovskaya E.A., Salnikov D.S., Amanova A.V. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2020. V. 63. N. 10. P. 4-10. DOI: 10.6060/ivkkt.20206310.6257.
Khazimullina Y.Z., Gimadieva A.R. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2022. V. 66. N 2. P. 36-44. DOI: 10.6060/ ivkkt.20236602.6652.
Sheibak V.M. Leucine, isoleucine, valine: biochemical basis for the development of new drugs. Grodno: Grod.st. med. Univ. 2014. 244 p. (in Russian).
Lyapina L.A., Shubina T.A., Myasoedov N.F., Grigorjeva M.E., Obergan T.Y., Andreeva L.A., Rogozinskaya E.J. // Ross. Fiziolog. Zhurn. im. I.M. Sechenova. 2019. V. 105. N 4. P. 492-500. DOI: 10.1134/S0869813919040022.
Santos Souza H.F., Marsiccobetre S., Souza R.O.O., Luevano-Martinez L.A., Silber A.M. // Exp. Parasitol. 2023. V. 249. 108499. DOI: 10.1016/j.exppara.2023.108499.
Wu T., Wang M., Ning F., Zhou S., Hu X., Xin H., Reilly S., Zhang X. // Pharmacol. Res. 2023. V. 187. 106604. DOI: 10.1016/j.phrs.2022.106604.
Sivanand S., Heiden M.G.V. // Cancer Cell. 2020. V. 37. N 2. P. 147-156. DOI: 10.1016/j.ccell.2019.12.011.
Li J., Zhou X., Takashi M., Todoroki K., Toyo’oka, Shi Q., Jin T., Min J.Z. // Clinica Chimica Acta. 2023. V. 545. 117367. DOI: 10.1016/j.cca.2023.117367.
Adade C.M., Figueiredo R.C.B.Q., De Castro S.L., Soares M.J. // Acta Tropica. 2007. V. 101. N 1. P. 69-79. DOI: 10.1016/j.actatropica.2006.12.006.
Mizuta H., Watanabe S., Sakurai Y., Nishiyama K., Furuta T., Kobayashi Y., Iwamura M. // Bioorg.Med. Chem. 2002. V. 10. N 3. P. 675-683. DOI: 10.1016/50968-0896(01)00323-6.
Haidukevich V.A., Khadarovich A.A., Popova L.A., Knizhnikov V.A. // Russ. J. Gen. Chem. 2022. V. 92. N 6. P. 955-959. DOI: 10.1134/s1070363222060068.
Haidukevich V.A., Popova L.A., Zubreichuk Z.P., Knizhnikov V.A. // Russ. J. Org. Chem. 2015. V. 51. N 5. P. 615-618. DOI: 10.1134/S1070428015050048.
Mikhalkin A.P. // Usp. Khim. 1995. V. 64. N 3. P. 275–292 (in Russian). DOI: 10.1070/RC1995v064n03ABEH000149.
Kuritsyn L.V., Kustova T.P., Sadovnikov A.I., Kalinina N.V., Klyuev M.V. Kinetics of acyl transfer reactions. Iva-novo: Ivan. St. Univ. 2006. 260 p. (in Russian).
Kochetova L. B., Kalinina N.V., Kustova T.P. // Russ. Chem. Bull. 2009. V. 58. N 4. P. 741-745. DOI: 10.1007/ s11172-009-0088-1.
Kochetova L.B., Kustova T.P. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2009. V. 52. N 5. P. 12-15 (in Russian).
Kustova T.P., Kochetova L.B., Kalinina N.V. // Russ. J. Gen. Chem. 2009. V. 79. N 5. P. 885-890. DOI: 10.1134/ S107036320905003Х.
Kalinina N.V., Kustova T.P., Kochetova L.B. // Russ. Chem. Bull. 2010. V. 59. N 5. P. 922-926. DOI: 10.1007/ s11172-010-0186-0.
Ishkulova N.R., Oparina L.E., Kochetova L.B., Kustova T.P., Kalinina N.V., Kuritsyn L.V. // Russ. J. Gen. Chem. 2010. V. 80. N 5. P. 964-967. DOI: 10.1134/ S1070363210050178.
Kustova T.P., Shcheglova N.G., Kochetova L.B. // Russ. J. Gen. Chem. 2010. V. 80. N 5. P. 972-975. DOI: 10.1134 /S1070363210050191.
Oparina L.E., Ishkulova N.R., Kochetova L.B., Kalinina N.V., Kuritsyn L.V., Kustova T.P. // ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2011. V. 54. N 2. P. 56-59 (in Russian).
Kochetova L.B., Kustova T.P., Kalinina N.V., Ishkulova N.R., LutsukV.V. // Theor. Exp. Chem. 2011. V. 47. N 1. P. 61-66. DOI: 10.1007/s11237-011-9186-x.
Kochetova L.B., Kalinina N.V., Grabchilova Yu.E., Simonova K.A., Kustova T.P. // Butlerov Soobshch. 2015. V. 43. N 7. P. 1-11 (in Russian). DOI: 10.37952/ROI-jbc-01/15-43-7-1.
Kochetova L.B., Kalinina N.V., Soloviyova D.S., Ditsina O.Yu., Kuritsyn L.V., Kustova T.P. // Butlerov Soobhsch. 2016. V. 45. N 1. P. 145-151 (in Russian). DOI: 10.37952/ ROI-jbc-01/16-45-1-145.
Kochetova L.B., Kustova T.P., Kuritsyn L.V. // Russ. J. Gen. Chem. 2018. V. 88. N 1. P. 80-85. DOI: 10.1134/ S1070363218010127.
Kustova T.P., Kochetova L.B. // Izv.AN Ser. Khim. 2019. V. 68. N 4. P. 809-816 (in Russian). DOI: 10.1007/s11172-019-2489-0.
Kustova T.P., Lokteva I.I., Kochetova L.B., Khachatryan D.S. // Russ. J. Org. Chem. 2020. V. 56. N 6. P. 1034-1040. DOI: 10.1134/S1070428020060111.
Kochetova L.B., Kustova T.P., Troitskaya U.V., Vasil’eva E.V., Moiseeva M.V. // Butlerov Soobshch. 2021. V. 67. N 7. P. 1-11 (in Russian). DOI: 10.37952/ROI-jbc-01/21-67-7-1.
Kustova T.P., Kochetova L.B., Khachatryan D.S. // Zhurn. Org. Khim. 2022. V. 58. N 4. P. 422-429 (in Rus-sian). DOI: 10.1134/S1070428022040078.
Kochetova L.B., Kustova T.P., Troitskaya U.V., Vasil’eva E.V., Khachatryan D.S. // Butlerov Soobshch. 2022. V. 71. N 7. P. 51-60 (in Russian). DOI: 10.37952/ROI-jbc-01/22-71-7-51.
Kochetova L.B., Paikova M.G., Kalinina N.V., Kustova T.P. // Butlerov Soobshch.. 2013. V. 35. N 9. P. 1-8 (in Rus-sian).
Vlasov V.M. // Russ. Chem. Rev. 2006. V. 75. N 9. P. 765-796. DOI: 10.1070/ RC2006v075n09ABEH003614.
Filimonov D.A., Lagunin A.A., Gloriozova T.A., Rudik A.V., Druzhilovskii D.S., Pogodin P.V., Poroikov V.V. // Chem. Het. Comp. 2014. V. 50. N 3. P. 444. DOI: 10.1007/s10593-014-1496-1.
