SYNTHESIS AND ANTIDEPRESSANT ACTIVITY OF 2-BROMO-1-(THIETAN-3-YL) IMIDAZOLE-4, 5-DICARBOXYLIC ACID DERIVATIVES


Ferkat Khaliullin, Irina Nikitina, Irina Nikitina, Anfisa Valieva, Anfisa Valieva, Albina Miftakhova, Albina Miftakhova, Leonard Khalilov, Ekaterina Mescheryakova, Leonard Khalilov

Abstract


Objective: Synthesis of the salts and diylidenehydrazidеs of 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid to evaluate the antidepressant activities.

Methods: The structures of the synthesised compounds were confirmed by elemental analysis and 1Н NMR spectral data. The melting points of the compounds were determined on a Stuart SMP30 apparatus. The X-ray diffraction data for compound IIc were obtained at room temperature on a Xcalibur Gemini Еos. The antidepressant activity was investigated in the tail suspension and forced swimming tests. The locomotor activity and anxiety were studied in the open field test.

Results: All synthesised compounds showed antidepressant activity after single intraperitoneal injection to male mice at doses equimolar to 10 mg/kg of imipramine. One of the compounds, 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid di[(4-hydroxy-3-methoxyphenyl) methylidenehydrazide], reduced the anxiety and decreased the locomotor activity at statistically significant levels. Other compounds did not have sedative and/or stimulating effects.

Conclusion: Among the synthesised 2-bromo-1-(thietan-3-yl) imidazole-4,5-dicarboxylic acid derivatives, compounds with marked antidepressant activity were identified. An obvious advantage of these products is low toxicity.


Keywords


Imidazole-4,5-dicarboxylic acid, Thietane, Diylidenehydrazidеs, Antidepressant activity

| PDF | HTML |

References


Negwer M, Scharnow HG. Organic-chemical drugs and their synonyms extensively enlarged. 9th ed. Vol. 1-7. Berlin: Wiley-VCH Verlag GmbH and Co; 2007.

Zhang N, Chen HM, Sood R, Kishna K, Fattom AI, Naso RB, et al. In vitro inhibition of the measles virus by novel ring-expanded ('fat') nucleoside analogues containing the imidazo [4,5-e] diazepine ring system. Bioorg Med Chem Lett 2002;12:3391-4.

Zhang P, Zhang N, Buckwold VE, Hosmane RS. Chemical and biological effects of substitution of the 2-position of ring-expanded ('fat') nucleosides containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system: The role of electronic and steric factors on glycosidic bond stability and anti-HCV activity. Bioorg Med Chem 2007;15:4933-45.

Premkumar T, Govindarajan S. Antimicrobial study of pyrazine, pyrazole and imidazole carboxylic acids and their hydrazinium salts. World J Microbiol Biotechnol 2005;21:479-80.

Nematollahi J, Guess W, Autian J. Imidazole carboxhydrazides. Chemistry and biological evalution. J Med Chem 1966;9:660-4.

Colman I, Ataullahjan A. Life course perspectives on the epidemiology of depression. J Can Psychiatr 2010;55:622-32.

Anki, Walia V. Influence of gender difference in the antidepressant effect of fluoxetine in mice in tail suspension test. Asian J Pharm Clin Res 2017;10:230-3.

Pendyala V, Babu Janga R, Suryadevara V. Phytochemical and pharmacological evaluation of commiphora mukul for antidepressant activity in albino mice. Asian J Pharm Clin Res 2017;10:360-3.

Agilent. Crys alis PRO. Agilent Technologies, Yarnton, Oxfordshire, England; 2012.

Sheldrick GM. A short history of SHELX. Acta Crystallogr Sect A: Found Adv 2008;A64:112-22.

Khaliullin FA, Valieva AR, Magadeeva GF. Hydrazinolysis of dimethyl 2-bromo-1-(thietan-3-yl)-1H-imidazole-4,5-dicarboxy-lates. Russ J Org Chem 2015;51:91-4.

Khaliullin FA, Valieva AR. Synthesis and structure of salts of 2-bromo-1-(thietanyl-3) imidazole-4,5-dicarboxylic acid. Bashkir Chem J 2013;20:34-6.

Khaliullin FA, Valieva AR, Magadeeva GF. Synthesis and structure of diylidenhydrazidеs of 2-bromo-1-(thietanyl-3)imidazole-4,5-dicarboxylic acid. Bashkir Chem J 2012;19:223-5.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985;85:367-70.

Schetinin EV, Baturin VA, Arushanyan EB, Ovanesov KB, Popov AV. Biorythmological approach to the forced swim evaluation as an experimental model of "depressive" condition. Pavlov J Higher Nerv Act 1989;5:958-64.

Sestakova N, Puzserova A, Kluknavsky M, Bernatova I. Determination of motor activity and anxiety-related behaviour in rodents: methodological aspects and role of nitric oxide. Interdiscip Toxicol 2013;6:126-35.

Gabidullin RA, Ivanova OA, Nikitina IL, Alekhin EK. Certificate of state registration of the computer №2008610170. Moscow; 2008.

Glantz S. Biomedical statistics, translation from English. Moscow: Practice; 1998.

Litchfield JT, Wilcoxon FT. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 1949;96:99-113.

Prozorovsky VB. Using the least-squares method for the analysis of probit mortality curves. Pharmakol Toksikol 1962;1:115-9.

Berezovskaya IV. Classification of substances with respect to acute toxicity for parenteral administration. Pharm Chem J 2003;37:139-41.




About this article

Title

SYNTHESIS AND ANTIDEPRESSANT ACTIVITY OF 2-BROMO-1-(THIETAN-3-YL) IMIDAZOLE-4, 5-DICARBOXYLIC ACID DERIVATIVES

Keywords

Imidazole-4,5-dicarboxylic acid, Thietane, Diylidenehydrazidеs, Antidepressant activity

DOI

10.22159/ijpps.2017v9i8.17613

Date

01-08-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 8, 2017 Page: 154-160

Online ISSN

0975-1491

Statistics

78 Views | 68 Downloads

Authors & Affiliations

Ferkat Khaliullin
Department of Pharmaceutical Chemistry, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Irina Nikitina
Department of Pharmacology № 1, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Irina Nikitina
Department of Pharmacology № 1, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Anfisa Valieva
Department of Pharmaceutical Chemistry, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Anfisa Valieva
Department of Pharmaceutical Chemistry, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Albina Miftakhova
Department of Pharmacology № 1, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Albina Miftakhova
Department of Pharmacology № 1, Bashkir State Medical University, Lenina Str., 3, 450008, Ufa, Russia

Leonard Khalilov
Laboratory of Structural Chemistry, Institute of Petrochemistry and Catalysis, Russian Academy of Science, Prospekt Oktyabrya, 141, 450075, Ufa, Russia

Ekaterina Mescheryakova
Laboratory of Structural Chemistry, Institute of Petrochemistry and Catalysis, Russian Academy of Science, Prospekt Oktyabrya, 141, 450075, Ufa, Russia

Leonard Khalilov
Laboratory of Structural Chemistry, Institute of Petrochemistry and Catalysis, Russian Academy of Science, Prospekt Oktyabrya, 141, 450075, Ufa, Russia


Article Tools



Refbacks

  • There are currently no refbacks.