Asian Journal of Research in Pharmaceutical Sciences

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Qsar and Docking Studies of Some Novel Piperine Analogues as Monoamine Oxidase Inhibitors


Affiliations
1 Krupanidhi College of Pharmacy, 12/1, ChikkaBellandur, Carmelaram Post, Varthur Hobli, Bangalore 560035, Karnataka., India
2 College of Pharmaceutical Sciences, Dayananda Sagar University, Kumarswamy Layout, Bengaluru-560078, India
     

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Piperine is an attractive target from natural sources for designing of novel compounds for many pharmacological activities. In present work, series of MAO inhibitors were taken and QSAR models were generated using MLRA. The best model were validated using test set, they exhibited r2 0.8427 and q2 0.7852 for MOA-B inhibitors; MAO-A inhibitors showed r2 0.7970 and q2 0.6657. Models. The QSAR models were used to design 70 new piperine analogue and docking studies were performed to check their inhibitory activity. Docking studies were performed using AutoDock, with proteins 2BXR and 2VZ2 for MAO-A and MAO-B inhibitory activity respectively. P12 and P11 for 2BXR showed best binding energy of -5.89 kcal/mol. and -6.43 kcal/mol respectively whereas P1078 and P1090 showed binding energy of -5.86 kcal/mol. and -8.56 kcal/mol for 2VZ2 respectively.

Keywords

Piperine, MAO-A, MAO- B inhibitors, QSAR, molecular docking, Auto Dock.
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  • Khom S, Strommer B, Schöffmann A, Hintersteiner J, Baburin I, Erker T, Schwarz T, Schwarzer C, Zaugg J, Hamburger M, Hering S. GABA A receptor modulation by piperine and a non-TRPV1 activating derivative. Biochemical Pharmacology 2013, 85(12):182736.

  • Kirtikar KR, Basu BD. Investigation towards new lead compounds from medicinally important plants. in: Indian Medicinal Plants Basu LM Publications Allahabad India 1933, 3(2):2131-2136.

  • Koul S, Koul JL, Taneja SC, Dhar KL, Jamwal DS, Singh K, Reen RK, Singh J. Strucutre-Activity Relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible Cytochrome P450 activity. Bioorganic and Medicinal Chemistry 2000, 8:251-268.

  • Agarwal O. Alkaloids In: Chemistry of organic natural products. 40th ed. Goal publishing house A unit of krishna prakashan media (p) Ltd. 2010.

  • Atal CK, Manavalan R, Nighojkar R, Sareen AN, Gupta OP. Studies on Piper chaba as a bioavailable agent. Indian Drugs 1980 17(9) 266-268.

  • Li S, Wang C, Wang M, Li W, Matsumoto K, Tang Y. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sciences, 2007, 80(15):1373-81.

  • Wattanathorn J, Chonpathompikunlert P, Muchimapura S, Priprem A, Tankamnerdthai O. Piperine the potential functional food for mood and cognitive disorders Food and Chemical Toxicology, 2008, 46(9):3106-10.

  • Kumar S, Singhal V, Roshan R, Sharma A, Rembhotkar G, Ghosh B. Piperine inhibits TNF-α induced adhesion of neutrophils to endothelial monolayer through suppression of NF-κB and IκB kinase activation. European Journal of Pharmacology, 2007, 575(1-3):177-86.

  • Vijayakumar R, Nalini N. Piperine an active principle from Piper nigrum modulates hormonal and apolipoprotein profiles in hyperlipidemic rats. Journal of Basic Clinical Physiology Pharmacology, 2006, 17(2):71-86.

  • Park B, Son D, Park Y, Kim T, Lee S. Antiplatelet effects of acid amides isolated from the fruits of Piper longum L. Phytomedicine, 2007, 14(12):853-5.

  • Manoharan S, Balakrishnan S, Menon V, Alias L, Reena A. Chemo preventive efficacy of curcumin and piperine during 7 12- dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Singapore Medical Journal, 2009, 50(2):139-46.

  • Kim S, Lee Y. Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model. Journal of Pharmacy and Pharmacology, 2009, 61(3):353-9.

  • Taqvi S, Shah A, Gilani A. Blood pressure lowering and vasomodulator effects of piperine. Journal of Cardiovascular Pharmacology, 2008, 52(5):452-8.

  • Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I, Yoshikawa M. Protective effects of amide constituents from the fruit of Piper chaba on D- galactosamine/TNF-alphainduced cell death in mouse hepatocytes. Bioorganic Medicinal Chemistry Letter, 2008, 18(6):2038-42.

  • Piyachaturawat P, Pholpramoolz C. Enhancement of fertilization by piperine in hamsters. Cell Biology International, 1997, 21(7):405-9.

  • Singh K, Kumar M, Pavadai E, Naran K, Warner DF, Ruminski PG, Chibale K. Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c. Bioorganic and Medicinal Chemistry Letters, 2014, 2985–2990.

  • Aukunuru J, Eedula K, Pasham V, Katla V, Reddy SK. Synthesis of novel piperonal derivatives and evaluation of their anticonvulsant activity using a nanoparticular formulation. International journal of pharmaceutical sciences and nanotechnology, 2009, 2(1):435-442.

  • Mary Sheeja TL, Mathew A, Varkey J. Design synthesis and pharmacological evaluation of isoxazole analogues derived from natural piperine. Asian journal of pharmaceutical and health sciences, 2012, 2(1):256-260.

  • Umadevi P, Kolli D, Venugopal DVR. Synthesis anticancer and antibacterial activities of piperine analogues. Medicinal Chemistry Research, 2013, 22:5466–5471.

  • Carrara VDS, Cunha-Junior EF, Torres-Santos EC, Correa AG,Monteiro JL, Demarchi IG, Lonardoni MVC, Cortez DAG. Antileishmanial activity of amides from Piper synthetic analogues. Revista Brasileira de Farmacognosia/Brazilian Journal of Pharmacognosy, 2013, 23(3):447-454.

  • Contingiba F, Regasini LO, Bolzani VS, Debonsi, Passerini GD, Cicarelli RMB, Kato MJ, Furlan M Piperamides and their derivatives as potential anti-trypanosomal agents. Medicinal Chemistry Research, 2009 18:703-711.

  • Shih JC, Chen K, Ridd MJ (1999) Monoamine oxidase: from genes to behavior. Annual Review of Neuroscience, 1999, 22:197-217.

  • Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC. cDNA cloning of human monoamine oxidase A and B: Molecular differences between two forms of the enzyme. Proceeding of National Academy of Science, 1988, 85:4934-4938.

  • Abell CW, Kwan SW. Molecular characterization of monoamine oxidase A and B. Progress in Nucleic Acids Research and Molecular Biology 2001, 65:129–156.

  • Jegham S, George P. Monoamine oxidase A and B inhibitors. Expert Opinion on Therapeutic Patents,1988, 8:1143—1150.

  • Pei YQ. A review of pharmacology and clinical uses of piperine and its derivatives. Epilepsia 1983, 24:177—182.

  • Al-Baghdadi OB, Prater NI, Van der Schyf, CJ, Geldenhuys WJ. Inhibition of monoamine oxidase by derivatives of piperine an alkaloid from the pepper plant Piper nigrum for possible use in Parkinson’s disease. Bioorganic and Medicinal Chemistry Letters 2012, 22 (23):7183-7188.

  • Mu LH, Wang B, Ren HY, Liu P , Guo DH, Wang FM, Bai L, Guo YS. Synthesis and inhibitory effect of piperine derivates on monoamine oxidase. Bioorganic and Medicinal Chemistry Letters 2012, 22(9):3343-3348.


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  • Qsar and Docking Studies of Some Novel Piperine Analogues as Monoamine Oxidase Inhibitors

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Authors

Sakshi Bhardwaj
Krupanidhi College of Pharmacy, 12/1, ChikkaBellandur, Carmelaram Post, Varthur Hobli, Bangalore 560035, Karnataka., India
Sonal Dubey
College of Pharmaceutical Sciences, Dayananda Sagar University, Kumarswamy Layout, Bengaluru-560078, India

Abstract


Piperine is an attractive target from natural sources for designing of novel compounds for many pharmacological activities. In present work, series of MAO inhibitors were taken and QSAR models were generated using MLRA. The best model were validated using test set, they exhibited r2 0.8427 and q2 0.7852 for MOA-B inhibitors; MAO-A inhibitors showed r2 0.7970 and q2 0.6657. Models. The QSAR models were used to design 70 new piperine analogue and docking studies were performed to check their inhibitory activity. Docking studies were performed using AutoDock, with proteins 2BXR and 2VZ2 for MAO-A and MAO-B inhibitory activity respectively. P12 and P11 for 2BXR showed best binding energy of -5.89 kcal/mol. and -6.43 kcal/mol respectively whereas P1078 and P1090 showed binding energy of -5.86 kcal/mol. and -8.56 kcal/mol for 2VZ2 respectively.

Keywords


Piperine, MAO-A, MAO- B inhibitors, QSAR, molecular docking, Auto Dock.

References