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. 2019 May 14;24(10):1857.
doi: 10.3390/molecules24101857.

Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5- a]thieno[2,3- e]pyridine Derivatives

Shiben Wang  1 , Hui Liu  2 , Xuekun Wang  3 , Kang Lei  4 , Guangyong Li  5 , Zheshan Quan  6
Affiliations

Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5- a]thieno[2,3- e]pyridine Derivatives

Shiben Wang et al. Molecules. .

Abstract

In this study, we synthetized a series of 5-aryl-4,5-dihydrotetrazolo[1,5-a]thieno[2,3-e]pyridine derivatives containing tetrazole and other heterocycle substituents, i.e., triazole, methyltriazole, and triazolone. The forced swim test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The compound 5-[4-(trifluoromethyl)phenyl]-4,5-dihydrotetrazolo[1,5-a]thieno[2,3-e]pyridine (4i) showed the highest antidepressant activity, with a reduced immobility time of 55.33% when compared with the control group. Using an open-field test, compound 4i was shown to not affect spontaneous activity of mice. The determination of in vivo 5-hydroxytryptamine (5-HT) concentration showed that compound 4i may have an effect in the mouse brain. The biological activities of all synthetized compounds were verified by molecular docking studies. Compound 4i showed significant interactions with residues of the 5-HT1A receptor homology model.

Keywords: 5-HT; FST; antidepressant; molecular docking studies; synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of compound I, Paroxetine, and target compounds 4a–p, 5, 6 and 7.
Scheme 1
Scheme 1
Synthesis of the target compounds. Reagents and conditions: (i) P2S5, CH3CN, 4–7 h; (ii) NH2NH2.H2O, CH3OH, reflux, 1 h; (iii) NaNO2, 5% HCl, 0–5 °C, 5 h; (iv) HC(OC2H5)3, 100 °C, 6 h; (v) CH3COOH, reflux, 2 h; (vi) NH2CONH2, 170 °C, 4 h.
Figure 2
Figure 2
Exploratory activity (counts) in the open-field test. The behavioral parameters were recorded for 3 min. Locomotion: number of line crossings; rearing: number of times seen standing on hind legs; grooming: number of modifications; 4i (40 mg/kg) was administered 60 min before the test. The values represent the mean ±SEM (n = 8).
Figure 3
Figure 3
(a) 3D model; (b) Ramachandran plot; (c) Binding pocket of compound 4i to 5-HT1A receptor; (d) Compound 4i showing interactions with residues of the 5-HT1A receptor.
See this image and copyright information in PMC

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References

    1. Badr S.M.I. Synthesis and anti-inflammatory activity of novel 2,5-disubstituted thiophene derivatives. Turk. J. Chem. 2010;35:131–143.
    1. Foroumadi A., Mansouri S., Kiani Z., Rahmani A. Synthesis and in vitro antibacterial evaluation of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl]piperazinyl quinolones. Eur. J. Med. Chem. 2003;38:851–854. doi: 10.1016/S0223-5234(03)00148-X. - DOI - PubMed
    1. Amer A.E., Sherif M.H., Assy M.G., Al-Omar M.A., Ragab I. Antiarrhythmic, serotonin antagonist and antianxiety activities of novel substituted thiophene derivatives synthesized from 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene-3-carboxamide. Eur. J. Med. Chem. 2010;45:5935–5942. doi: 10.1016/j.ejmech.2010.09.059. - DOI - PubMed
    1. Fadda A.A., Abdel-Latif E., El-Mekawy R.E. Synthesis of some new arylazothiophene and arylazopyrazole derivatives as antitumor agents. J. Pharm. Pharmacol. 2012;3:148–157. doi: 10.4236/pp.2012.32022. - DOI
    1. Ali K.A., Abdalghfar H.S., Mahmoud K., Ragab E.A. Synthesis and antitumor activity of new Polysubstituted Thiophenes and 1,3,4-thiadiazoles incorporating 2,6-pyridine moieties. J. Heterocycl. Chem. 2013;50:1157–1164. doi: 10.1002/jhet.1613. - DOI