Synthesis of 2,4-dihydroxychalcone Derivatives as Potential Antidepressant Effect

L.-P. Guan; D.-H. Zhao; Y. Chang; Z.-S. Wen; L.-M. Tang; F.-F. Huang

doi:10.1055/s-0032-1333229

Drug Research, Table of Contents

Drug Res (Stuttg) 2013; 63(01): 46-51
DOI: 10.1055/s-0032-1333229

Original Article

Synthesis of 2,4-dihydroxychalcone Derivatives as Potential Antidepressant Effect

L.-P. Guan

¹Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, China

,

D.-H. Zhao

²Jilin Medical College, Jilin City, Jilin, China

,

Y. Chang

¹Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, China

³College of Pharmacy, Yanbian University, Yanji, Jilin, China

,

Z.-S. Wen

¹Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, China

,

L.-M. Tang

¹Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, China

,

F.-F. Huang

¹Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan, China

› Author Affiliations

Abstract

In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system.

Key words

2,4-dihydroxychalcone derivatives - synthesis - antidepressant activity - 5-Hydroxytryptophan - yohimbine

Full Text

References

References
1 Meyer C. Depressive disorders were the fourth leading cause of global disease burden in the year 2000. Evid Based Ment Health 2004; 7: 123-127
2 Lopez AD, Murray CC. The global burden of disease, 1990–2020. Nat Med 1998; 4: 1241-1243
3 Thase MS. Evaluating antidepressant therapies: remission as the optimal outcome. J Clin Psychiatry 2003; 64 (Suppl. 13) 18-25
4 Thase ME, Corya SA, Osuntokun O et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry 2007; 68: 224-236
5 Hirschfeld RM. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J Clin Psychiatry 1999; 60: 326-335
6 Go ML, Wu X, Liu XL. Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 2005; 12: 481-499
7 Batovska D, Parushev St, Slavova A et al. study on the substituents effects of a series of synthetic chalcones against the yeast Candida albicans. Eur J Med Chem 2007; 42: 87-92
8 Lahtchev KL, Batovska DI, Parushev StP et al. Antifungal activity of chalconed: A mechanistic study using various yeast strains. Eur J Med Chem 2008; 43: 2220-2228
9 Trivedi JC, Bariwal JB, Upadhyay KD et al. Improved and rapid synthesis of new coumarinyl chalcone derivatives and their antivira activity. Tetrahedron Lett 2007; 48: 8472-8474
10 Vogel S, Barbic M, Jürgenliemk G et al. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. Eur J Med Chem 2010; 45: 2206-2213
11 Kimura Y, Baba K. Antitumor and antimetastatic activities of angelica keiskei roots, part 1: Isolation of an active substance, xanthoangelol. Int J Cancer 2003; 106: 429-437
12 Zhao DH, Sui X, QU YL et al. Synthesis and Studies on Antidepressant Effect of 5,7-Dihydroxyflavanone Derivatives. Asian J of Chem 2011; 23: 1129-1132
13 Zhao DH, Zhang YZ, Zheng ZH. Synthesis and Studies on Antidepressant Effect of 2′,4′-dihyoxylchalcone. Shi Zhen Medicine and Materia Medica Research 2010; 21: 1115-1116
14 Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229: 327-336
15 Porsolt RD. Antidepressants: Neurochemical Behavioral and Clinical Perspectives. In: Enna SJ, Malick JB, Richelson E, (eds.). Raven Press; New York: 1981. 129-139
16 Elhwuegi AS. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 435-451
17 Millan MJ. The role of monamines in the actions of established and “novel” antidepressant agents: a critical review. Eur J Pharmacol 2004; 200: 371-384
18 Nishida J, Kawabata J. DPPH radical scavenging reaction of hydroxy- and methoxychalcones. Biosci Biotechnol Biochem 2006; 70: 193-202
19 Sui X, Zhao DH, Qu YL et al. Synthesis and studies on antidepressant activity of 2′,4′,6′-trihydroxychalcone derivatives. Med Chem Res 2011; 21: 1290-1296
20 Guan LP, Yin XM, Quan HM et al. Synthesis of hydroxylated chalcones and related derivatives. Chinese J Org Chem 2004; 24: 1274-1277
21 Steru L, Chermat R, Thierry B et al. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 1985; 85: 367-370
22 Hanna MM, Eida NM, Georgea RF et al. Synthesis of some tropane derivatives of anticipated activity on the reuptake up norepinephrine and/or serotonin. Bioorg Med Chem 2007; 15: 7765-7772
23 Goodwin GM, Green AR, Johnson P. 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice. Br J Pharmacl 1984; 83: 235-242
24 Nishida J, Kawabata J. DPPH radical scavenging reaction of hydroxy- and methoxychalcones. Biosci Biotechnol Biochem 2006; 70: 193-202
25 Zhao LM, Jin HS, Sun LP et al. Synthesis and evaluation of antiplatellet activity of trihydroxychalcone derivatives. Bioorg Med Chem Lett 2005; 15: 5027-5029
26 Bourin M, Chenu F, Ripoll N et al. Aproposal of decision tree to screen putative antidepressants using forced swim and tail suspension tests. Behav Brain Res 2005; 164: 266-269
27 Petit-Demouliere B, Chenu F, Bourin M. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl.) 2005; 177: 245-255
28 Schechter LE, Ring RH, Beyer CE et al. Innovative approaches for the development of antidepressant drugs: current and future strategies. NeuroRx 2005; 2: 590-611
29 Richelson E. The clinical relevance of antidepressant interaction with neurotransmitter transporters and teceptors. Psychopharmacol Bull 2002; 36: 133-150
30 Corne SJ, Pickering RW, Warner BT. A method for assessing the effects of drugs on the central actions of 5-hydroxytryoptamene. Br J Pharmacol Chemother 1963; 20: 106-120
31 Lapin IP. Adrenergic nonspecific potentiation of yohimbine toxicity in mice by antidepressants and related drugs and antiyohimbine action of antiadrenergic and serotonergic drugs. Psychopharmacology 1980; 70: 179-185
32 Luo ZP. Beijing: People’s Medical Publishing House; 2005