Search of potential antidiabetic drugs in range of 5-(phenoxymethylene)-4-R-1,2,4-triazole-3-thions
DOI:
https://doi.org/10.14739/2409-2932.2016.2.70814Keywords:
1, 2, 4-triazole, Hypoglycemic Effect, Alloxan Induced DiabetesAbstract
The modern pharmaceutical market has countless number of hypoglycemic drugs. But information about domestic antidiabetic drugs based on 1,2,4-triazole nucleus is almost unknown. Researches in this field of science are an important task for scientists of synthetic and organic chemistry.
Aim. That’s why the purpose of our work is the search for potential hypoglycemic drugs among 3-thioderivatives of 5-(phenoxymethylene)-4-R-1,2,4-triazoles-3-thiones (R=C2H5, C6H5) using screening method and next detailed pharmacological study of the most promising compounds.
Methods and methods. Hypoglycemic effect of 1,2,4-triazole derivatives has been evaluated using intraperitoneal glucose tolerance test (IPGTT), which has been reproduced by glucose administering to animals at a dose of 2 g/kg of rat body weight. The glucose level has been determined in blood after 30 minutes. Determination was carried out with the glucose oxidase method using the express analyzer «Accu-Chek Active». The hypoglycemic effect has been studied for active substances using alloxan induced diabetes, which has been reproduced on white nonlinear rats. The alloxan induced diabetes was modeled with intraperitoneal administration of alloxan monohydrate solution at a dose of 75 mg/kg in a 5% citrate buffer solution (pH 4.5), after the 24 h of food deprivation (with free access to water).
Results. The research results have been processed with modern statistical analysis methods on PC using the standard package of Microsoft Office 2010 software (Microsoft Excel) and «STATISTICA® for Windows 6.0». A number of compounds which can decrease the level of glucose have been identified based on result of IPGTT. We have established the dependence of the hypoglycemic effect on the chemical structure.
Conclusions. The median effective dose has been calculated for most active compound with probit analysis.
References
Kolesnyk, Yu. M., Kaplaushenko, A. H,. Knish, Ye. H., Panasenko, O. І., Shcherbak, M. O., & Sameliuk, Yu. H. (2014) Pokhіdnі 4-amіno ta 3-tіo-1,2,4-trіazolu yak potentsіinі lіkarskі zasoby [Derivatives of 4-amino-3 and then-1,2,4-triazole as potential drugs]. Zaporіzhzhya. [in Ukrainian].
Shcherbak, M. O., Kaplaushenko, A. H., Trzhetsynskyi, S. D., & Klevanova, V. S. (patentee) (2015) Patent 97632 Ukraїna, C07D 249/00, A61K31/41. ferum(II) 2-(5-(3-nіtrofenіl)-4-amіno-1,2,4-trіazol-3-іltіo)atsetat, shcho viyavlyaє gіpoglіkemіchnu aktivnіst' [iron (II) 2-(5-(3-nitrophenyl)-4-amino-1,2,4-triazole-3-ylthio)acetate, which shows hypoglycemic activity]. Biuleten, 6. [in Ukrainian].
Shcherbak, M. O., Kaplaushenko, A. H., Trzhetsynskyi, S. D., & Klevanova, V. S. (patentee) (2015) Patent 97634 Ukraina, C07D 249/00, A61K31/41. MPK6: S07D 249/00, A61K 31/41. 2-((3-merkapto-5-(3-nitrofenil)-4N-1,2,4-triazol-4-il-imino)metyl)fenol, shcho vyiavliaie hipohlikemichnu aktyvnist [2-((3-mercapto-5-(3-nitrophenyl)-4H-1,2,4-triazol-4-yl-imino)methyl)phenol which shows hypoglycemic activity]. Biuleten, 6. [in Ukrainian].
Chandrashekar, A., Eswarappa, B., & Yadav D. B. (2014) Synthesis, invitro and invivo anti-hyperglycemic activity of 1,2,4-triazolebenzylidene and 1,3,4-thiadiazole derivatives. International Journal of PharmTech Research, 4, 1245–1255.
Kees, K., Fitzgerald, J., Steiner, K., Matter, J., Mihan, B., Tosi, T., et al. (1996). New potent antihyperglycemic agents in db/db mice: synthesis and structure-activity relationship studies of (4-substituted benzyl) (trifluoromethyl)pyrazoles and –pyrazolones. Journal of Medicinal Chemistry, 39(20), 3920–3928. doi: 10.1021/jm960444z.
Dave, K. R., & Katyare, S. S. (2002) Effect of alloxan-induced diabetes on serum and cardiac butyrylcholinesterases in the rat. Journal of Endocrinology, 175(1), 241–250.
Garcia, M., Moran, A., Calama, E., Martín, M. L., Barthelmebs, M., & Román, L. S. (2005) Diabetes-induced changes in the 5-hydroxytryptamine inhibitory receptors involved in the pressor effect elicited by sympathetic stimulation in the pithed rat. British Journal of Pharmacology, 145(5), 593–601. doi: 10.1038/sj.bjp.0706216.
Akinola, O., Gabriel, M., Suleiman, A.-A., & Olorunsogbon, F. (2012) Treatment of alloxan-induced diabetic rats with metformin or glitazones is associated with amelioration of hyperglycaemia and neuroprotection. The Open Diabetes Journal, 5(1), 8–12.
Thrilochana, P., Nimain, C. S., Kuntal, H., & Ramachandran, S. (2014) Synthesis and biological evaluation of new Thiadiazole analogues for anti-diabetic activity against Alloxan induced diabetes. Journal of Pharmacy Research, 8, 1559–1562.
Downloads
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)
