Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities

Authors

DOI:

https://doi.org/10.14739/2409-2932.2021.1.226742

Keywords:

3-benzylxanthine, acetohydrazide, physicochemical properties

Abstract

One of the most important tasks of our indigenous pharmaceutical science is the necessity for new medicines because existing drugs are characterized by various side effects, resistance, high toxicity, and so on. New bioactive molecule synthesis utilizes substances of natural origin as well as chemically modified ones. Thus, the researcher’s attention is mainly focused on 3-,7-,8-substituted derivatives of the natural heterocyclic xanthine system, which possess a wide range of pharmacological action. Synthesis of a novel of (3-benzyl-8-propylxanthin-7-yl)acetohydrazides with antimicrobial and diuretic activities described in the paper.

The aim of this work is to develop efficient methods for synthesis of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives, and to study their physical-chemical properties.

Materials and methods. Two-hour boiling of propyl 2-(3-benzyl-8-propylxanthine-7-yl)acetate by excess hydrazine hydrate in propan-2-ol medium have yielded the key the key intermediate 2-(3-benzyl-8-propylxanthine-7-yl)acetohydrazide. Further transformation of the latter has led to formation of corresponding acetohydrazide derivatives achieved by the reaction with aliphatic, aromatic, heterocyclic aldehydes, and ketones. The structure and the relative configuration of the synthesized compounds were elucidated by analyzing their physical-chemical data.

Results. The synthesis and optimization of reaction conditions of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives were conducted. The identification of all synthesized compounds was aided by various physical-chemical methods (thin layer chromatography, elemental analysis, IR, and 1H NMR spectroscopy).

Conclusions. As a result of synthetic research the preparative synthesis method of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives possessing antimicrobic, and diuretic activities was developed.

References

Ojha, R., Singh, J., Ojha, A., Singh, H., Sharma, S., & Nepali, K. (2017). An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015). Expert opinion on therapeutic patents, 27(3), 311-345. https://doi.org/10.1080/13543776.2017.1261111

Marx, D., Schnakenburg, G., Grimme, S., & Müller, C. E. (2019). Structural and Conformational Studies on Carboxamides of 5,6-Diaminouracils-Precursors of Biologically Active Xanthine Derivatives. Molecules, 24(11), 2168. https://doi.org/10.3390/molecules24112168

Marx, D., Wingen, L. M., Schnakenburg, G., Müller, C. E., & Scholz, M. S. (2019). Fast, Efficient, and Versatile Synthesis of 6-amino-5-carboxamidouracils as Precursors for 8-Substituted Xanthines. Frontiers in chemistry, 7, 56. https://doi.org/10.3389/fchem.2019.00056

Mikhal’chenko, E. K., Аleksandrova, K. V., & Levich S. V. (2016). Syntez i fizyko-khimichni vlastyvosti 3-benzyl-8-propilksantynu ta yoho vodorozchynnykh solei [Synthesis and physical-chemical properties of 3-benzyl-8-propylxanthine and its water-soluble salts]. Current issues in pharmacy and medicine: science and practice, (1), 26-30. https://doi.org/10.14739/2409-2932.2016.1.62005

Aleksandrova, K. V., Levich, S. V., Belenichev, I. F., & Shkoda, A. S. (2015). Research of energotropic properties of 3-benzylxanthine derivative-prospective neuroprotector. International Journal of Pharmacy, 5(1), 1-4.

Suravajhala, R., Poddar, R., Nallapeta, S., & Ullah, S. (2014). Xanthine Derivatives: A Molecular Modeling Perspective. In P. B. Kavi Kishor, R. Bandopadhyay, P. Suravajhala (Eds.), Agricultural Bioinformatics (pp. 283-291). Springer, New Delhi. https://doi.org/10.1007/978-81-322-1880-7_17

Monteiro, J. P., Alves, M. G., Oliveira, P. F., & Silva, B. M. (2016). Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks. Molecules, 21(8), 974. https://doi.org/10.3390/molecules21080974

Levich, S. V., Shkoda, O. S., Kamyshnyi, O. M., Aleksandrova, K. V., & Polischuk, N. M. (2013). 2-(3-benzyl-8-metylksantyn-7-il)-N-[(1E,2E)-3-(5-nitrofuran-2-il)prop-2-en-1-iliden]-atsetohid-razyd, yakyi vyiavliaie antymikrobnu diiu [2-(3-benzyl-8-methylxanthine-7-yl)-N'-[(1E,2E)-3-(5-nitrofuran-2-YL)prop-2-ene-1-yliden]-acetohydrazide exhibiting antimicrobial action]. Ukraine Patent UA 83840.

Aleksandrova, K. V., Mykhalchenko, Ye. K., & Levich, S. V. (2017). Vyvchennia protymikrobnykh ta protyhrybkovykh vlastyvostei 7-zamishchenykh 3-benzyl-8-propilksantyniv [Study of antimicrobial and antifungal properties of 7-substituted 3-benzyl-8-propylxanthines]. Medychnyi forum, (10), 9-12. [in Ukrainian].

Way2Drug. (n.d.). PASS Online. Way2Drug.com. http://www.pharmaexpert.ru/PASSOnline

Aleksandrova, K. V., Mykhalchenko, Ye. K., Pruhlo, Ye. S., & Sinchenko, D. M. (2018). Hidrazyd 3-benzyl-8-propilksantyn-7-il atsetatnoi kysloty, yakyi vyiavliaie diuretychnu diiu [3-Benzyl-8-propylxanthin-7-yl acetic acid hydrazide, which has a diuretic effect]. Ukraine Patent UA 128510. https://base.uipv.org/searchINV/search.php?action=viewdetails&IdClaim=251158

Mykhalchenko, Ye., Aleksandrova, К., Shkoda, O., & Pruglo, Ye. (2019). Prospective biological active compounds among 7-substituted of 3-benzyl-8-propylxanthines for treatment of metabolic syndrome pathologies. EUREKA: Health Sciences, (5), 52-58. https://doi.org/10.21303/2504-5679.2019.00988

Downloads

Published

2021-03-18

How to Cite

1.
Aleksandrova KV, Mykhalchenko YK, Shkoda OS, Vasyliev DA. Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities. Current issues in pharmacy and medicine: science and practice [Internet]. 2021Mar.18 [cited 2024Mar.28];14(1):17-22. Available from: http://pharmed.zsmu.edu.ua/article/view/226742

Issue

Section

Original research