Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities
DOI:
https://doi.org/10.14739/2409-2932.2021.1.226742Keywords:
3-benzylxanthine, acetohydrazide, physicochemical propertiesAbstract
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
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
