Skip to main content
SpringerLink
Log in

Design, synthesis and antidepressant activities of some novel fatty acid analogues

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

The present study deals with the optimization of some novel heterocyclic compounds containing two biological scaffolds such as long alkyl/alkenyl side chain of fatty acids and five-membered azoles named as 1,3,4-oxadiazole, 1,2,4-triazole and 1,3,4-thiadiazoles as antidepressant agents. In-silico docking studies have been carried out for the tested compounds into the crystal structure of human mono amine oxidase-B using GLIDE integrated Maestro (9.3) version. Five analogues exhibited higher XP G-Scores than selegeline. Also, it was verified by in vivo antidepressant screening, where two of the compounds PA-2 and GLA-2 showed significant antidepressant activity. Drug likelinesss and comparative bioactive analysis for the analogues are done using Qik.Prop 3.4.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A (2003) Insights into the mode of inhibition of human mitochondrial mono amine oxidase B from high resolution structures. Proc Natl Acad Sci USA 100(17):9750–9755

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chimenti F, Bolasco A, Manna F, Secci D, Chimenti P, Granese A, Bafeni O, Turini P, Cirilli R (2006) Synthesis, biological evaluation and 3D-QSAR of 1,3,5-trisubstituted-4,5-dihydro-(1H)-pyrazole derivatives as potent and highly selective monoamine oxidase A inhibitors. Curr Med Chem 13:1411–1428

    Article  CAS  PubMed  Google Scholar 

  • Fava M (2001) Augmentation and combination strategies in treatment resistant depression. J Clin Psychiatry 62:4–11

    CAS  PubMed  Google Scholar 

  • Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini A, Jalali H, Peet M (2008) Comparision of therapeutic effects of omega-3-fatty acid eocosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. J Psychiatry 42:192–198

    Google Scholar 

  • Jubie S, Shanish Antony A, Sikdar Pranabesh, Kalirajan R, Gomathy S, Gowramma B, Elango K (2011) Synthesis and biological evaluation of some Schiff bases of [4-(amino)-5-phenyl-l-4H-1,2,4-triazole-3-thiol. Pak J Pharm Sci 24–2:109–112

    Google Scholar 

  • Jubie S, Gayathri R, Kalirajan R (2012a) Synthesis and neuropharmacological evaluation of some novel quinoxaline 2,3-dione derivatives. Sci World J. doi:10.1100/2012/718023

    Google Scholar 

  • Jubie S, Nilesh P, Dhanabal SP, Kalirajan R, Muruganandham N, Shanish Antony A (2012b) Synthesis, antidepressant and antimicrobial activities of some novel stearic acid analogues. Eur J Med Chem 54:931–935

    Article  CAS  PubMed  Google Scholar 

  • Jubie S, Dhanabal SP, Afzal Azam Md, Muruganandham N, Kalirajan R, Elango K (2013) Synthesis and characterization of some novel fatty acid analogues: a preliminary investigation against human lung carcinoma cell line. Lipids Health Dis 12:45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kalirajan R, Vivek K, Sankar S, Jubie S (2012) Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their anti oxidant and anticancer activities as topo isomerase ii inhibitors. Eur J Med Chem 56:217–224

    Article  CAS  PubMed  Google Scholar 

  • Kane JM, Dudley MW, Sorrenson SM, Miller FP (1998) 2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. J Med Chem 31:1253–1258

    Article  Google Scholar 

  • Kaplancikli ZA, Ozdemir A, Zitouni GT, Altintop MD (2010) New pyrazoline derivatives and their antidepressant activity. Eur J MedChem 45:4383–4387

    Article  CAS  Google Scholar 

  • Kumar S, Bawa S, Drabu S, Gupta H, Machwal L, Kumar R (2011) Synthesis, antidepressant and antifungal evaluation of novel 2-chloro-8-methylquinoline amine derivatives. Eur J Med Chem 46:670–675

    Article  CAS  PubMed  Google Scholar 

  • Laino CH, Fonseca C, Speziale NS, Slobodianik N, Reines A (2010) Potentiation of omega-3 fatty acid antidepressant-like effects with low non-antidepressant doses of fluoxetine and mirtazapine. Eur J Pharmacol 648:117–126

    Article  CAS  PubMed  Google Scholar 

  • Lakwani L, Sudheer KT, Veerendra SP, Rajendra PA, Prem N, Pradeep P (2007) Omega-3 fatty acids have antidepressant activity in forced swimming test in Wistar Rats. Acta Pol Pharm Drug Res 64(3):271–276

    Google Scholar 

  • Lin EH, Von Korff M, Katon W, Bush T, Simon GE, Walker E, Robinson P (1994) The role of the primary care physician in patient’s adherence to antidepressant therapy. Med Care 33:67–74

    Article  Google Scholar 

  • Meraj K, Manoj Kumar M, Christina NB, Nidhi D, Shahbazi S, Bhaskar M (2012) Molecular modelling, docking and ADMET studies towards development of novel Disopyramide analogs for potential inhibition of human voltage gated sodium channel proteins. Bio Information 8(23):1139–1146

    Google Scholar 

  • Nemets B, Stahl Z, Belmaker RH (2002) Omega-3-treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 159:477–479

    Article  PubMed  Google Scholar 

  • Norinder U, Bergstorm CAS (2006) Prediction of ADMET properties. Chem Med Chem 1:920–927

    Article  CAS  PubMed  Google Scholar 

  • Palaska E, Aytemir M, Uzbay IT, Erol D (2001) Synthesis and antidepressant activities of some 3,5diphenyl-2-pyrazolines. Eur J Med Chem 36:539–543

    Article  CAS  PubMed  Google Scholar 

  • Papakostas GI (2005) Augmentation of standard antidepressants and atypical antipsychotic agents for treatment-resistant major depressive disorder. Essent Psychopharmacol 6:209–220

    PubMed  Google Scholar 

  • Rakofsky JJ, Holtzheimer PE, Nemeroff CB (2009) Emerging targets for antidepressant therapies. Curr Opin Chem Biol 13:291–302

    Article  CAS  PubMed  Google Scholar 

  • Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnel D, Hayward RC, Heatherley SV, Chistian LM, McNaughton SA, Ness AR (2008) No effect of n-3 long chain poly unsaturated fatty acid supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 99(2):421–423

    Article  CAS  PubMed  Google Scholar 

  • Roopa K, Asif MK, Anupriya G, Chong YS, Loganath A (2010) cheminformatics-based drug design approach for identification of inhibitors targeting the characteristic residues of MMP-13 hemopexin domain. PLoS One 5(8):e12494

    Article  Google Scholar 

  • Sarva MC, Romeo G, Guerrera F, Siracusa M, Saierno L, Russo F, Goegan A, Mennini T (2002) [1,2,4]Triazole derivatives as 5-HT(1A) serotonin receptor ligands. Bioorg Med Chem 10:313–323

    Article  CAS  PubMed  Google Scholar 

  • Shri R, Bhutani KK, Sharma A (2010) A new anxiolytic fatty acid from Aethusa cynapium. Fitoterapia 81:1053–1057

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, JSS College of Pharmacy (A Constituent College of JSS University, Mysore), Rocklands, Udhagamandalam, Ooty, 643001, Tamilnadu, India

    Selvaraj Jubie, Mohammed Afzal Azam & Rajagopal Kalirajan

  2. Department of Pharmacognosy and Phytopharmacy, JSS College of Pharmacy (A Constituent College of JSS University, Mysore), Udhagamandalam, Ooty, 643001, Tamilnadu, India

    Palaniswamy Dhanabal

  3. Department of Pharmacology, JSS College of Pharmacy (A Constituent College of JSS University, Mysore), Udhagamandalam, Ooty, 643001, Tamilnadu, India

    Natarajan Satish Kumar & Nilesh Ambhore

Authors
  1. Selvaraj Jubie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Palaniswamy Dhanabal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammed Afzal Azam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natarajan Satish Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nilesh Ambhore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajagopal Kalirajan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Selvaraj Jubie.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jubie, S., Dhanabal, P., Azam, M.A. et al. Design, synthesis and antidepressant activities of some novel fatty acid analogues. Med Chem Res 24, 1605–1616 (2015). https://doi.org/10.1007/s00044-014-1235-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1235-2

Keywords

Search

Navigation