Synthesis of new thiazolo[3,2-a]pyrimidine derivatives and in silico analysis of their bioactivity
https://doi.org/10.29235/1561-8331-2021-57-4-456-462
Abstract
An effective method of synthesis thiazolo[3,2-a]pyrimidine derivatives was developed and the compounds with n-pentyl or β-acetoxycyclopropyl as well as fluorescent benzo[f]coumarin substituents were obtained with yields 60 % and more. Using computational (in silico) approaches we demonstrated the ability of the obtained compounds to permeate lipid bilayer as well as their affinity to some protein kinases (compounds 4 and 6 bind with a protein kinase AKT1 with PDB code 3о96; Autodock Vina-computed energy of binding (Ebind) values were -10.9 and -10.6 kcal/mol, respectively), acethylcholine esterase and some human cytochromes P450 (for P450 3A4, pdb 5vcd, Ebind -12.3 kcal/mol).
About the Authors
I. V. Mineeva
Belarusian State University
Belarus
Belarus
Iryna V. Mineeva – Ph. D. (Chemistry), Associate Professor, Doctoral Student of the Department of Organic Chemistry
14, Leningradskaya Str., 220006, Minsk, Republic of Belarus
Y. V. Faletrov
Belarusian State University; Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Yaroslav V. Faletrov – Ph. D. (Chemistry), Associate Professor, Doctoral Student of the Department of Macromolecular Compounds, Leading Researcher
14, Leningradskaya Str., 220006, Minsk, Republic of Belarus
V. A. Starovoytova
Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Victoria A. Starovoytova – Research Assistant
14, Leningradskaya Str., 220006, Minsk, Republic of Belarus
V. M. Shkumatov
Belarusian State University; Research Institute for Physical Chemical Problems of the Belarusian State University
Belarus
Belarus
Vladimir M. Shkumatov – Corresponding Member of the National Academy of Sciences of Belarus, D. Sc. (Biology), Professor, Head of the Laboratory
14, Leningradskaya Str., 220006, Minsk, Republic of Belarus
References
1. Kaur R., Chaudhary S., Kumar K., Gupta M. K., Rawal R. K. Recent synthetic and medicinal perspectives of dihydropyrimidinones: а review. European Journal of Medicinal Chemistry, 2017, vol. 132, pp. 108–134. https://doi.org/10.1016/j.ejmech.2017.03.025
2. Salem M. A. I., Marzouk M. I., Salem M. S., Alshibani G. A. One-pot synthesis of 1,2,3,4-tetrahydropyrimidin-2(1H)-thione derivatives and their biological activity. Journal of Heterocyclic Chemistry, 2016, vol. 53, no. 2, pp. 545–557. https://doi.org/10.1002/jhet.2358
3. Sekhar T., Thriveni P., Venkateswarlu A., Daveedu T., Peddanna K., Sainath S. B. One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies. Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy, 2020, vol. 231, pp. 118056. https://doi.org/10.1016/j.saa.2020.118056
4. Ma C., Wang Y., Dong F., Wang Z., Zhao Y., Shan Y., Gu W., Wang S. Synthesis and antitumor activity of isolongifoleno[7,8-d]thiazolo[3,2-a]pyrimidine derivatives via enhancing ROS level. Chemical Biology and Drug Design, 2019, vol. 94, pp. 1457–1466. https://doi.org/10.1111/cbdd.13522
5. Sun Y., Fu R., Lin S., Zhang J., Ji M., Zhang Y., Wu D., Zhang K., Tian H., Zhang M., Sheng L., Li Y., Jin J., Chen X., Xu H. Discovery of new thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives as orally active phosphoinositide 3-kinase inhibitors. Bioorganic and Medicinal Chemistry, 2021, vol. 29, pp. 115890. https://doi.org/10.1016/j.bmc.2020.115890
6. Mahgoub M. Y., Elmaghraby A. M., Harb A. A., Ferreira da Silva J. L., Justino G. C., Marques M. M. Synthesis, crystal Structure, and biological evaluation of fused thiazolo[3,2-a]pyrimidines as new acetylcholinesterase inhibitors. Molecules, 2019, vol. 24, no. 12, pp. 2306. https://doi.org/10.3390/molecules24122306
7. Murahari M., Prakash K. V., Peters G. J., Mayur Y. C. Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular docking studies. European Journal of Medicinal Chemistry, 2017, vol. 139, pp. 961–981. https://doi.org/10.1016/j.ejmech.2017.08.023
8. Valasani K. R., Chaney M. O., Day V. W, Yan S. S. Acetylcholinesterase inhibitors: structure based design, synthesis, pharmacophore modeling and virtual screening. Journal of the Chemical Information and Modeling, 2013, vol. 53, no. 8, pp. 2033–2046. https://doi.org/10.1021/ci400196z
9. Ali F., Khan K. M., Salar U., Iqbal S., Taha M., Ismail N. H., Perveen S., Wadood A., Ghufran M., Ali B. Dihydropyrimidones: as novel class of β-glucuronidase inhibitors. Bioorganic and Medicinal Chemistry, 2016, vol. 24, no. 16, pp. 3624–3635. https://doi.org/10.1016/j.bmc.2016.06.002
10. Lauroa G., Strocchia M., Terracciano S., Bruno I., Fischer K., Pergola C., Werz O., Riccio R., Bifulco G. Exploration of the dihydropyrimidine scaffold for the development of new potential anti-inflammatory agents blocking prostaglandin E2 synthase-1 enzyme (mPGES-1). European Journal of Medicinal Chemistry, 2014, vol. 80, pp. 407–415. https://doi.org/doi.org/10.1016/j.ejmech.2014.04.061
11. Babu K. R., Rao V. K., Kumar Y. N., Polireddy K., Subbaiah K. V., Bhaskar M., Lokanatha V., Raju C. N. Identification of substituted [3, 2-a] pyrimidines as selective antiviral agents: Molecular modeling study. Antiviral Research, 2012, vol. 95, no. 2, pp. 118–127. https://doi.org/doi.org/10.1016/j.antiviral.2012.05.010
12. Sari O., Roy V., Metifiot M., Marchand C., Pommier Y., Bourg S., Bonnet P., Schinazi R. F., Agrofoglio L. A. Synthesis of dihydropyrimidine α, γ-diketobutanoic acid derivatives targeting HIV integrase. European Journal of Medicinal Chemistry, 2015, vol. 104, pp. 127–138. https://doi.org/doi.org/10.1016/j.ejmech.2015.09.015
13. Sawant R. L., Sarode V. I., Jadhav G. D., Wadekar J. B. Synthesis, molecular docking, and cardioprotective activity of 2-methylthio-1,4-dihydropyrimidines. Medicinal Chemistry Research, 2012, vol. 21, no. 8, pp. 1825–1832. https://doi.org/10.1007/s00044-011-9700-7
14. Zhou B., Li X., Li Y., Xu Y., Zhang Z., Zhou M., Zhang X., Liu Z., Zhou J., Cao C., Yu B., Wang R. Discovery and development of thiazolo[3,2-a]pyrimidinone derivatives as general inhibitors of Bcl-2 family proteins. Chem. Med. Chem., 2011, vol. 6, no. 5, pp. 904–921. https://doi.org/10.1002/cmdc.201000484
15. Kolb S., Mondеsert O., Goddard M.-L., Jullien D., Villoutreix B. O., Ducommun B., Garbay C., Braud E. Development of novel thiazolopyrimidines as CDC25B phosphatase inhibitors. Chem. Med. Chem., 2009, vol. 4, no. 4, pp. 633–648. https://doi.org/10.1002/cmdc.200800415
16. Ershov P. V., Yablokov E., Zgoda V., Mezentsev Y., Gnedenko O., Kaluzhskiy L., Svirid A., Gilep A., Usanov S. A., Ivanov A. A new insight into subinteractomes of functional antagonists: thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases. Cell Biology International, 2021, vol. 45, no. 6, pp. 1175–1182. https://doi.org/10.1002/cbin.11564
17. Novikova L.A., Faletrov Y. V.,Kovaleva I.E., Mauersberger, S.,Luzikov V.N., Shkumatov V. M.From the structure and function of steroid biosynthetic enzymes to new genetically engineered technologies. Uspekhi Biologicheskoi Khimii = Biological chemistry reviews, 2009, vol. 49, pp. 159–208 (in Russian).
18. Zhuo X., Wang Y. Z., Yeung K. S., Zhu J., Huang X. S., Parcella K. E., Eastman K. J., Kadow J. F., Meanwell N. A., Shu Y. Z., Johnson B. M. Bioactivation of cyclopropyl rings by P450: an observation encountered during the optimisation of a series of hepatitis C virus NS5B inhibitors. Xenobiotica, 2018, vol. 48, no. 12, pp. 1215–1226. https://doi.org/10.1080/00498254.2017.1409915
19. Keri R. S., Sasidhar B. S., Nagaraja B. M., Santos M. A. Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents. European Journal of Medicinal Chemistry, 2015, vol. 100, pp. 257–269. https://doi.org/10.1016/j.ejmech.2015.06.017
20. Lomize A. L., Pogozheva I. D., Mosberg H. I. Anisotropic solvent model of the lipid bilayer. 2. Energetics of insertion of small molecules, peptides, and proteins in membranes. Journal of Chemical Information and Modeling, 2011, vol. 51, no. 4, pp. 930–946. https://doi.org/ 10.1021/ci200020k
21. Jin C.-H., Jun K.-Y., Lee E., Kim S., Kwon Y., Kim K., Na Y. Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3, 2-a]pyrimidine-6-carboxylate analogues as a new scaffold for protein kinase casein kinase 2 inhibitor. Bioorganic and Medicinal Chemistry, 2014, vol. 22, no. 17, pp. 4553–4565. https://doi.org/doi.org/10.1016/j.bmc.2014.07.037
Review
Views: 687
Email this article 