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Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Review Article

Modification in the Natural Bioactive Molecule: Piperine; A Continuing Source for the Drug Development

Author(s): Bhawna Chopra*, Ashwani K. Dhingra and Deo N. Prasad

Volume 16, Issue 6, 2020

Page: [714 - 725] Pages: 12

DOI: 10.2174/1573407215666190318125023

Price: $65

Abstract

Background: Piperine, a bioactive alkaloid was a well-known component which was used traditionally to treat a variety of disorders.

Objective: The present review is to discuss the modified piperine or piperic acid analogs or its derivatives to explore the potential of piperine. Piperine or piperic acid had potentials as antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal, immunomodulatory and many more for drug development. So modification in natural molecule piperine generates numerous derivatives or analogues which may be found beneficial in drug development.

Methods: A literature survey has been carried out to determine the real potential of piperine and its modified analogs.

Results: It has been scrutinized that piperine and its derivatives possess valuable components with good therapeutic potential.

Conclusion: Thus, this review aims to provide knowledge as well as to explore the excellent potential of piperine, piperic acid, piperine derived compounds/ analogs which may further, after performing toxicity studies, and other parameters, be helpful in the design and development of novel drug candidates against numerous disease conditions and thus it paves way for further work in exploring the potential to treat the patients with obesity and skin related disorders.

Keywords: Efflux pump, piperine, piperic acid, in silico, fat fighter, stereochemical factors.

Graphical Abstract

[1]
Chopra, B.; Dhingra, A.K.; Kapoor, R.P.; Prasad, D.N. Piperine and its various physicochemical and biological aspects: A review. Open Chem. J., 2016, 3, 75-96.
[http://dx.doi.org/10.2174/1874842201603010075]
[2]
Chinta, G.; Syed, S.B.; Coumar, M.S.; Periyasamy, L. Piperine: A comprehensive review of pre-clinical and clinical investigations. Curr. Bioact. Compd., 2015, 11, 156-169.
[http://dx.doi.org/10.2174/1573407211666150915214425]
[3]
Geissmann, T.A.; Crout, D.H.G. Organic chemistry of secondary plant metabolism San Francisco: Freeman, Cooper Company 170, 1969.
[4]
Simon, K.O.; Henry, O.E. Piperine-type amides: Review of the chemical and biological characteristics. Int. J. Chem., 2013, 5(3), 99-122.
[5]
Bird, C.R.; Smith, T.A. The biosynthesis of coumarylagmatine in barley seedlings. Phytochemistry, 1981, 20, 2345-2346.
[http://dx.doi.org/10.1016/S0031-9422(00)82662-X]
[6]
Bird, C.R.; Smith, T.A. Agmatine Coumaroyl Transferase (ACT) from barley seedlings. Phytochemistry, 1983, 22, 2401-2403.
[http://dx.doi.org/10.1016/0031-9422(83)80127-7]
[7]
Negrel, J.; Martin, C. The biosynthesis of feruloyltyramine in nicotianatabacum. Phytochemistry, 1984, 23, 2797-2801.
[http://dx.doi.org/10.1016/0031-9422(84)83018-6]
[8]
Negrel, J.; Jeandet, P. Metabolism of tyramine and feruloyltyramine in TMV inoculated leaves of Nicotianatabacum. Phytochemistry, 1987, 26, 2185-2190.
[http://dx.doi.org/10.1016/S0031-9422(00)84681-6]
[9]
Semler, U.; Schmidtberg, G.; Gross, G.G. Synthesis of piperoyl-CoA-thioester. Z. Naturforsch., 1987, 42c, 1070-1074.
[http://dx.doi.org/10.1515/znc-1987-9-1011]
[10]
Semler, U.; Gross, G.G. Distribution of piperine in vegetative parts of Piper nigrum. Phytochemistry, 1988, 27, 1566.
[http://dx.doi.org/10.1016/0031-9422(88)80249-8]
[11]
Rugheimer, L. Kunstlichespiperin. Ber. Dtsch. Chem. Ges., 1882, 15, 1390-1391.
[12]
Grewe, R.; Freist, W.; Neumann, H.; Kersten, S. About the ingredients of black pepper. Chem. Ber., 1970, 103, 3752-3770.
[http://dx.doi.org/10.1002/cber.19701031204]
[13]
Wenkert, E.; Cochran, D.W.; Hagaman, E.W.; Lewis, R.B.; Schellet, F.M. Carbon-13 nuclear magnetic resonance spectroscopy of naturally occurring substances. VII. Carbon-13 nuclear magnetic resonance spectroscopy with the aid of a paramagnetic shift agent. JACS, 1971, 93, 6271-6273.
[http://dx.doi.org/10.1021/ja00752a049]
[14]
Grynpas, M.; Lindley, P.F. The crystal and molecular structure of 1-piperoylpiperidine. Acta Crystallogr. B, 1975, 31, 2663-2667.
[http://dx.doi.org/10.1107/S0567740875008412]
[15]
Rogoski, J.M.; Nagornyy, P.A. Stereoselective Synthesis of Piperine via a Horner Wadsworth-Emmons Reaction., http://www.geocities.ws/justin_m_r/papers/piperine.pdf
[16]
Schobert, R.; Siegfrieda, S.; Gordon, G.J. Three-component synthesis of (E)-α,β-unsaturated amides of the piperine family. J. Chem. Soc. Perkin. Trans., 2001, 119, 2393-2397.
[http://dx.doi.org/10.1039/b105745f]
[17]
Koul, S.; Koul, J.L.; Taneja, S.C.; Dhar, K.L.; Jamwal, D.S.; Singh, K.; Reen, R.K.; Singh, J. Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities. Bioorg. Med. Chem., 2000, 8(1), 251-268.
[http://dx.doi.org/10.1016/S0968-0896(99)00273-4] [PMID: 10968285]
[18]
Chatterjee, A.; Dutta, C.P. Alkaloids of Piper longum Linn. I. Structure and synthesis of piperlongumine and piperlonguminine. Tetrahedron, 1967, 23(4), 1769-1781.
[http://dx.doi.org/10.1016/S0040-4020(01)82575-8] [PMID: 6047519]
[19]
Singh, J.; Dhar, K.L.; Atal, C.K. Studies on the Genus Piper-IX. Structure of trichostachine, an alkaloid from piper trichostachyon. Tet. Letts., 1969, 56, 4975-4978.
[http://dx.doi.org/10.1016/S0040-4039(01)88862-6]
[20]
Singh, I.P.; Choudhary, A. Piperine and derivatives: Trends in structure- activity relationships. Curr. Top. Med. Chem., 2015, 15(17), 1722-1734.
[http://dx.doi.org/10.2174/1568026615666150427123213] [PMID: 25915609]
[21]
Qu, H.; Lv, M.; Xu, H. Piperine: Bioactivities and structural modifications. Mini Rev. Med. Chem., 2015, 15(2), 145-156.
[http://dx.doi.org/10.2174/1389557515666150101100509] [PMID: 25553428]
[22]
Vanessa, S.C.; Edezio, F.C.J.; Eduardo, C.T.S.; Arlene, G.C.; Julia, L.M.; Izabel, G.D.; Maria, V.; Campana, L.; Dioge-nes, A.G.C. Antileishmanial activity of amides from Piper amalagoand synthetic analogs. Braz. J. Pharmacog., 2013, 23(3), 447-454.
[http://dx.doi.org/10.1590/S0102-695X2013005000022]
[23]
Singh, I.P.; Jain, S.K.; Kaur, A.; Singh, S.; Kumar, R.; Garg, P.; Sharma, S.S.; Arora, S.K. Synthesis and antileishmanial activity of piperoyl-amino acid conjugates. Eur. J. Med. Chem., 2010, 45(8), 3439-3445.
[http://dx.doi.org/10.1016/j.ejmech.2010.04.033] [PMID: 20546981]
[24]
Ferreira, C.; Soares, D.C.; Barreto-Junior, C.B.; Nascimento, M.T.; Freire-de-Lima, L.; Delorenzi, J.C.; Lima, M.E.F.; Atella, G.C.; Folly, E.; Carvalho, T.M.U.; Saraiva, E.M.; Pinto-da-Silva, L.H. Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis. Phytochemistry, 2011, 72(17), 2155-2164.
[http://dx.doi.org/10.1016/j.phytochem.2011.08.006] [PMID: 21885074]
[25]
Fernandes, Í.A.; de Almeida, L.; Ferreira, P.E.; Marques, M.J.; Rocha, R.P.; Coelho, L.F.; Carvalho, D.T.; Viegas, C., Jr Synthesis and biological evaluation of novel piperidine-benzodioxole derivatives designed as potential leishmanicidal drug candidates. Bioorg. Med. Chem. Lett., 2015, 25(16), 3346-3349.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.068] [PMID: 26094119]
[26]
Umadevi, P.; Deepti, K.; Durvasula, V.R.V. Synthesis, anti-cancer and antibacterial activities of piperine analogs. Med. Chem. Res., 2013, 2(11), 5466-5471.
[http://dx.doi.org/10.1007/s00044-013-0541-4]
[27]
Zied, Z.; Emna, B.; Nadia, B.S.; Youssef, G.; Adel, S. Anti-oxidant and antimicrobial activities of various solvent extracts, piperine and piperic acid from Piper nigrum, LWT - Food. Sci. Tech. (Paris), 2013, 50, 634-641.
[28]
Mishra, S.; Narain, U.; Mishra, R.; Misra, K. Design, development and synthesis of mixed bioconjugates of piperic acid-glycine, curcuminglycine/ alanine and curcumin-glycine-piperic acid and their antibacterial and antifungal properties. Bioorg. Med. Chem., 2005, 13(5), 1477-1486.
[http://dx.doi.org/10.1016/j.bmc.2004.12.057] [PMID: 15698763]
[29]
Dubey, S.K.; Sharma, A.K.; Narain, U.; Misra, K.; Pati, U. Design, synthesis and characterization of some bioactive conjugates of curcumin with glycine, glutamic acid, valine and demethylenated piperic acid and study of their antimicrobial and antiproliferative properties. Eur. J. Med. Chem., 2008, 43(9), 1837-1846.
[http://dx.doi.org/10.1016/j.ejmech.2007.11.027] [PMID: 18201805]
[30]
Aanandhi, M.V.; Mishra, P.S.; George, S.; Chaudhary, R. Synthesis, antimicrobial and sedative hypnotic activity of cinnamoylureas. Int. J. Pharm. Tech. Res., 2011, 3(1), 99-103.
[31]
Durvasula, V.R.; Venugopal, N.S.Y.; Parimi, U. Synthesis, of novel piperine analogs of dipeptidyl boronic acid as antimicrobial and anticancer agents. Med. Chem., 2014, 4, 9.
[32]
Manayi, A.; Nabavi, S.M.; Setzer, W.N.; Jafari, S. Piperine as a potential anti-cancer agent: A review on preclinical studies. Curr. Med. Chem, 2018, 25(37), 4918-4928.
[http://dx.doi.org/10.2174/0929867324666170523120656] [PMID: 28545378]
[33]
Sattarinezhad, E.; Bordbar, A.K.; Fani, N. Piperine derivatives as potential inhibitors of Survivin: An in silico molecular docking. Comput. Biol. Med., 2015, 63, 219-227.
[http://dx.doi.org/10.1016/j.compbiomed.2015.05.016] [PMID: 26093789]
[34]
Mishra, S.; Kapoor, N.; Mubarak Ali, A.; Pardhasaradhi, B.V.V.; Kumari, A.L.; Khar, A.; Misra, K. Differential apoptotic and redox regulatory activities of curcumin and its derivatives. Free Radic. Biol. Med., 2005, 38(10), 1353-1360.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.01.022] [PMID: 15855053]
[35]
Wani, N.A.; Singh, S.; Farooq, S.; Shankar, S.; Koul, S.; Khan, I.A.; Rai, R. Amino acid amides of Piperic Acid (PA) and 4-Ethylpiperic Acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus. Bioorg. Med. Chem. Lett., 2016, 26(17), 4174-4178.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.062] [PMID: 27503686]
[36]
Khan, I.A.; Mirza, Z.M.; Kumar, A.; Verma, V.; Qazi, G.N. a Phytochemical Potentiator of Ciprofloxacin against Staphylococcus aureus Antimicro. Agents Chemother., 2006, 50(2), 810-812.
[37]
Kumar, A.; Khan, I.A.; Koul, S.; Koul, J.L.; Taneja, S.C.; Ali, I.; Ali, F.; Sharma, S.; Mirza, Z.M.; Kumar, M.; Sangwan, P.L.; Gupta, P.; Thota, N.; Qazi, G.N. Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J. Antimicrob. Chemother., 2008, 61(6), 1270-1276.
[http://dx.doi.org/10.1093/jac/dkn088] [PMID: 18334493]
[38]
Sangwan, P.L.; Koul, J.L.; Koul, S.; Reddy, M.V.; Thota, N.; Khan, I.A.; Kumar, A.; Kalia, N.P.; Qazi, G.N. Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors. Bioorg. Med. Chem., 2008, 16(22), 9847-9857.
[http://dx.doi.org/10.1016/j.bmc.2008.09.042] [PMID: 18848780]
[39]
Chopra, B.; Dhingra, A.K.; Dhar, K.L. Synthesis and characterization of piperine analogs as potent Staphylococcus aureus nora efflux pump inhibitors. Chemical Methodologies, 2018, 3, 126-136.
[40]
Tripathi, A.; Misra, K.; Kesharwani, R.K. Study of some piperine analogues on drugs efflux by targeting P-glycoprotein, an in silico approach. Lett. Drug Des. Discov., 2016, 13, 952-961.
[http://dx.doi.org/10.2174/1570180813999160830102312]
[41]
Ali, Y.; Alam, M.S.; Hamid, H.; Husain, A.; Bano, S.; Dhulap, A.; Kharbanda, C.; Nazreen, S.; Haider, S. Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents. Eur. J. Med. Chem., 2015, 92, 490-500.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.001] [PMID: 25596479]
[42]
Yasir, A.; Ishtiaq, S.; Jahangir, M.; Ajaib, M.; Salar, U.; Khan, K.M. Biology-Oriented Synthesis (BIOS) of piperine derivatives and their comparative analgesic and antiinflammatory activities. Med. Chem., 2018, 14(3), 269-280.
[http://dx.doi.org/10.2174/1573406413666170623083810] [PMID: 28641526]
[43]
Khom, S.; Strommer, B.; Schöffmann, A.; Hintersteiner, J.; Baburin, I.; Erker, T.; Schwarz, T.; Schwarzer, C.; Zaugg, J.; Hamburger, M.; Hering, S. GABAA receptor modulation by piperine and a non-TRPV1 activating derivative. Biochem. Pharmacol., 2013, 85(12), 1827-1836.
[http://dx.doi.org/10.1016/j.bcp.2013.04.017] [PMID: 23623790]
[44]
Sharma, S.; Kumar, M.; Sharma, S.; Nargotra, A.; Koul, S.; Khan, I.A. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J. Antimicrob. Chemother., 2010, 65(8), 1694-1701.
[http://dx.doi.org/10.1093/jac/dkq186] [PMID: 20525733]
[45]
Hanumantharao, G.R.; Gupta, S.; Prasad, A.K.; Boll, P.M.; Wengei, J.; Biswas, G.; Singh, S.K.; Sharma, N.K.; Bisht, K.S.; Parmar, V.S. Methylenedioxyphenyl substituted compounds from piper species as inhibitors of liver microsome-mediated aflatoxln Bi-DNA binding in vitro. Bioorg. Med. Chem. Lett., 1995, 5(15), 1567-1572.
[http://dx.doi.org/10.1016/0960-894X(95)00272-U]
[46]
Qu, H.; Yu, X.; Zhi, X.; Lv, M.; Xu, H. Natural-product-based insecticidal agents 14. Semisynthesis and insecticidal activity of new piperine- based hydrazone derivatives against Mythimna separata Walker in vivo. Bioorg. Med. Chem. Lett., 2013, 23(20), 5552-5557.
[http://dx.doi.org/10.1016/j.bmcl.2013.08.053] [PMID: 24018189]
[47]
Vanderlucia, F.P.; Luiz, C.A.B.; Antonio, J.D.; Dorila, P.V.; Marcelo, C.P. Synthesis and insecticidal activity of new amide derivatives of piperine. Pest Manag. Sci., 2000, 56, 168-174.
[http://dx.doi.org/10.1002/(SICI)1526-4998(200002)56:2<168:AID-PS110>3.0.CO;2-H]
[48]
da Silva Ferreira, W.; Freire-de-Lima, L.; Saraiva, V.B.; Alisson-Silva, F.; Mendonça-Previato, L.; Previato, J.O.; Echevarria, A.; de Lima, M.E. Novel 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: Chemical and biological studies. Bioorg. Med. Chem., 2008, 16(6), 2984-2991.
[http://dx.doi.org/10.1016/j.bmc.2007.12.049] [PMID: 18226906]
[49]
Ribeiro, T.S.; Freire-de-Lima, L.; Previato, J.O.; Mendonça-Previato, L.; Heise, N.; de Lima, M.E. Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi. Bioorg. Med. Chem. Lett., 2004, 14(13), 3555-3558.
[http://dx.doi.org/10.1016/j.bmcl.2004.04.019] [PMID: 15177472]
[50]
Franklim, T.N.; Freire-de-Lima, L.; de Nazareth Sá Diniz, J.; Previato, J.O.; Castro, R.N.; Mendonça-Previato, L.; de Lima, M.E. Design, synthesis and trypanocidal evaluation of novel 1,2,4-triazoles-3- thiones derived from natural piperine. Molecules, 2013, 18(6), 6366-6382.
[http://dx.doi.org/10.3390/molecules18066366] [PMID: 23760033]
[51]
Jingfen, H.; Gereltu, B.; Ruke, B.; Zharigetu, S.; Narisu, B.; Xuesi, C.; Xiabin, J. Synthesis and anti-hyperlipidemic activity of a novel starch piperinic ester. Carbohydr. Polym., 2008, 71, 441-447.
[http://dx.doi.org/10.1016/j.carbpol.2007.06.014]
[52]
Erdenebaatar, S.; Gereltu, B.; Sun, Z. The preparation and antihyperlipidaemic assay of piperlonguminine in vivo. Phytochem. Lett., 2013, 6, 101-105.
[http://dx.doi.org/10.1016/j.phytol.2012.12.002]
[53]
Harish, G.; Venkateshappa, C.; Mythri, R.B.; Dubey, S.K.; Mishra, K.; Singh, N.; Vali, S.; Bharath, M.M.S. Bioconjugates of curcumin display improved protection against glutathione depletion mediated oxidative stress in a dopaminergic neuronal cell line: Implications for Parkinson’s disease. Bioorg. Med. Chem., 2010, 18(7), 2631-2638.
[http://dx.doi.org/10.1016/j.bmc.2010.02.029] [PMID: 20227282]
[54]
Al-Baghdadi, O.B.; Prater, N.I.; Van der Schyf, C.J.; Geldenhuys, W.J. Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson’s disease. Bioorg. Med. Chem. Lett., 2012, 22(23), 7183-7188.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.056] [PMID: 23102654]
[55]
Han, M.; Ma, X.; Jin, Y.; Zhou, W.; Cao, J.; Wang, Y.; Zhou, S.; Wang, G.; Zhu, Y. Synthesis and structure-activity relationship of novel cinnamamide derivatives as antidepressant agents. Bioorg. Med. Chem. Lett., 2014, 24(22), 5284-5287.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.050] [PMID: 25442321]
[56]
Mu, L.H.; Wang, B.; Ren, H.Y.; Liu, P.; Guo, D.H.; Wang, F.M.; Bai, L.; Guo, Y.S. Synthesis and inhibitory effect of piperine derivates on monoamine oxidase. Bioorg. Med. Chem. Lett., 2012, 22(9), 3343-3348.
[http://dx.doi.org/10.1016/j.bmcl.2012.02.090] [PMID: 22475561]
[57]
Nandakumar, N.; Muthuraman, S.; Gopinath, P.; Nithya, P.; Gopas, J.; Kumar, R.S. Synthesis of coumaperine derivatives: Their NF-κB inhibitory effect, inhibition of cell migration and their cytotoxic activity. Eur. J. Med. Chem., 2017, 125, 1076-1087.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.047] [PMID: 27810594]
[58]
Huan, Q.; Min, L.; Xiang, Y.; Xihong, L.; Hui, X. Discovery of some piperine-based Phenylsulfonylhydrazone derivatives as potent botanically narcotic agents Nature. Sci. Rep., 2015, 5, 13077.
[59]
Venkatasamy, R.; Faas, L.; Young, A.R.; Raman, A.; Hider, R.C. Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation. Bioorg. Med. Chem., 2004, 12(8), 1905-1920.
[http://dx.doi.org/10.1016/j.bmc.2004.01.036] [PMID: 15051059]
[60]
Figueredo, A.S.; de Oliveira, M.G.; Safadi, G.M.V.V.; de Paula da Silva, C.H.T.; da Silva, V.; Taft, C.A.; de Aquino, B.G.L. The natural alkaloid piperine and its acid and ester synthetic derivatives are acetylcholinesterase inhibitors. Curr. Phys. Chem., 2015, 5, 294-300.
[http://dx.doi.org/10.2174/187794680504160308115710]
[61]
Park, U.H.; Jeong, H.S.; Jo, E. Y.; Park, T.; Yoon, S. K.; Kim, E. J.; Jeong, J.C.; Um, S, J. Piperine, a component of black pepper, inhibits adipogenesis by antagonizing PPARγ Activi-ty in 3T3-L1 Cells. J. Agric. Food Chem., 2012, 60, 3853.
[http://dx.doi.org/10.1021/jf204514a] [PMID: 22463744]
[62]
American Chemical Society. Unmasking black pepper’s secrets as a fat fighter Science Daily, 2012.www.sciencedaily.com/releases/2012/05/120502123520

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