Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

A Review of Chemistry and Pharmacology of Piperidine Alkaloids of Pinus and Related Genera

Author(s): Lav Singh, Atul K. Upadhyay, Pooja Dixit, Arpit Singh, Divyanshu Yadav, Apurv Chhavi, Suraj Konar, Ravi Prakash Srivastava, Shivaraman Pandey, Hari Prasad Devkota, Praveen C. Verma and Gauri Saxena*

Volume 23, Issue 9, 2022

Published on: 12 August, 2021

Page: [1132 - 1141] Pages: 10

DOI: 10.2174/1389201022666210812123815

Price: $65

Abstract

Background: Pinus belongs to the family Pinaceae, represented by several species across the globe. Various parts of the plant including needles are rich in biologically active compounds, such as thunbergol, 3-carene, cembrene, α-pinene, quercetin, xanthone. Of all the alkaloids, the piperidine group is one of the important component and holds considerable medicinal importance.

Methods: The group of alkaloids was initially identified from the genus Piper through which a large variety of piperidine molecules have been extracted. The planar structure of this heterocyclic nucleus enables acetamide groups to be added at various ring configurations.

Results: Piperidines have gained considerable importance. The broad range of its therapeutic application has paved a way for researchers to implant the nucleus from time to time in diversified pharmacophores and establish new profile.

Discussion: Biological functions of piperidine metabolites have been mostly examined on a limited scale, and that most of the findings are preliminary. We have tried to present various clinical applications of piperidine alkaloids in this study that researchers have already attempted to demystify with time.

Conclusion: We have also illustrated different types of piperidine structures and their sources in different members of the family Pinaceae with special emphasis on Pinus. Given the importance of the piperidine nucleus, the study will enable the researchers to produce scaffolds of highest therapeutic efficacy.

Keywords: Pinus, Piperidine, heterocyclic, therapeutic, pharmacophores, chemistry

« Previous Next »
Graphical Abstract

[1]
Farjon, A. World checklist and bibliography of conifers; Royal Botanic Gardens, 2001.
[2]
Gernandt, D.S.; López, G.G.; García, S.O.; Liston, A. Phylogeny and classification of Pinus. Taxon, 2005, 54, 29-42.
[http://dx.doi.org/10.2307/25065300]
[3]
El Omari, N.; Ezzahrae Guaouguaou, F.; El Menyiy, N.; Benali, T.; Aanniz, T.; Chamkhi, I.; Balahbib, A.; Taha, D.; Shariati, M.A.; Zengin, G.; El-Shazly, M.; Bouyahya, A. Phytochemical and biological activities of Pinus halepensis mill., and their ethnomedicinal use. J. Ethnopharmacol., 2021, 268, 113661.
[http://dx.doi.org/10.1016/j.jep.2020.113661] [PMID: 33276057]
[4]
Parmar, V.S.; Jain, S.C.; Bisht, K.S.; Jain, R.; Taneja, P.; Jha, A.; Tyagi, O.D.; Prasad, A.K.; Wengel, J.; Olsen, C.E. Phytochemistry of the genus Piper. Phytochemistry, 1997, 46, 597-673.
[http://dx.doi.org/10.1016/S0031-9422(97)00328-2]
[5]
Seigler, D.S. Plant secondary metabolism; Kluwer Academic Publishers: New York, 1999.
[6]
Green, B.T.; Lee, S.T.; Panter, K.E.; Brown, D.R. Piperidine alkaloids: human and food animal teratogens. Food Chem. Toxicol., 2012, 50(6), 2049-2055.
[http://dx.doi.org/10.1016/j.fct.2012.03.049] [PMID: 22449544]
[7]
Leete, E.; Juneau, K.N. Biosynthesis of pinidine. J. Am. Chem. Soc., 1969, 91(20), 5614-5618.
[http://dx.doi.org/10.1021/ja01048a031] [PMID: 5808502]
[8]
Leete, E.; Lechleiter, J.C.; Carver, R.A. Determination of the ‘starter’acetate unit in the biosynthesis of pinidine. Tetrahedron Lett., 1975, 16, 3779-3782.
[http://dx.doi.org/10.1016/S0040-4039(00)91271-1]
[9]
Tallent, W.H.; Stromberg, V.L.; Horning, E.C. Pinus alkaloids. The alkaloids of P. SabinianaDougl. and related species. J. Am. Chem. Soc., 1955, 77, 6361-6364.
[http://dx.doi.org/10.1021/ja01628a084]
[10]
Schneider, M.J.; Montali, J.A.; Hazen, D.; Stanton, C.E. Alkaloids of Picea. J. Nat. Prod., 1991, 54, 905-909.
[http://dx.doi.org/10.1021/np50075a031]
[11]
Schneider, M.J.; Stermitz, F.R. Uptake of host plant alkaloids by root parasitic pedicularis species. Phytochemistry, 1990, 29, 1811-1814.
[http://dx.doi.org/10.1016/0031-9422(90)85021-7]
[12]
Todd, F.G.; Stermitz, F.R.; Blokhin, A.V. Piperidine alkaloid content of Piceapungens (Colorado Blue Spruce). Phytochemistry, 1995, 40, 401-406.
[http://dx.doi.org/10.1016/0031-9422(95)00213-Q]
[13]
Tawara, J.N.; Blokhin, A.; Foderaro, T.A.; Stermitz, F.R.; Hope, H. Toxic piperidine alkaloids from pine (Pinus) and spruce (Picea) trees. New structures and a biosynthetic hypothesis. J. Org. Chem., 1993, 58, 4813-4818.
[http://dx.doi.org/10.1021/jo00070a014]
[14]
Stermitz, F.R.; Kamm, C.D.; Tawara, J.N. Piperidine alkaloids of spruce (Picea) and Fir (Abies) species. Biochem. Syst. Ecol., 2000, 28, 177-181.
[http://dx.doi.org/10.1016/S0305-1978(99)00054-X]
[15]
Stermitz, F.R.; Tawara, J.N.; Boeckl, M.; Pomeroy, M.; Foderaro, T.A.; Todd, F.G. Piperidine alkaloid content of Picea (Spruce) and Pinus (Pine). Phytochemistry, 1994, 35, 951-953.
[http://dx.doi.org/10.1016/S0031-9422(00)90645-9]
[16]
Kasé, Y.; Okano, Y.; Miyata, T.; Kataoka, M.; Yonehara, N. The production of piperidine from pipecolic acid in the rat brain. Life Sci., 1974, 14(4), 785-791.
[PMID: 4823631]
[17]
Brown, W.V.; Moore, B.P. Defensive alkaloids of Cryptolaemus montrouzieri (Coleoptera: Coccinellidae). Aust. J. Chem., 1982, 35, 1255-1261.
[http://dx.doi.org/10.1071/CH9821255]
[18]
Gerson, E.A.; Kelsey, R.G.; St Clair, J.B. Genetic variation of piperidine alkaloids in Pinus ponderosa: a common garden study. Ann. Bot. (Lond.), 2009, 103(3), 447-457.
[http://dx.doi.org/10.1093/aob/mcn228] [PMID: 19010800]
[19]
Virjamo, V.; Fyhrquist, P.; Koskinen, A.; Lavola, A.; Nissinen, K.; Julkunen-Tiitto, R. 1,6-dehydropinidine is an abundant compound in Picea abies (Pinaceae) sprouts and 1,6-dehydropinidine fraction shows antibacterial activity against Streptococcus equi Subsp. equi. Molecules, 2020, 25(19), 4558.
[http://dx.doi.org/10.3390/molecules25194558] [PMID: 33036142]
[20]
Schneider, M.J.; Brendze, S.; Montali, J.A. Alkaloids of Picea breweriana. Phytochemistry, 1995, 39, 1387-1390.
[http://dx.doi.org/10.1016/0031-9422(95)00147-Y]
[21]
Hill, R.K.; Chan, T.H.; Joule, J.A. The stereochemistry of pinidine. Tetrahedron, 1965, 21(1), 147-161.
[http://dx.doi.org/10.1016/S0040-4020(01)82210-9] [PMID: 5879338]
[22]
Tallent, W.H.; Horning, E.C. The structure of pinidine. J. Am. Chem. Soc., 1956, 78, 4467-4469.
[http://dx.doi.org/10.1021/ja01598a074]
[23]
Bennett, R.N.; Wallsgrove, R.M. Secondary metabolites in plant defence mechanisms. New Phytol., 1994, 127(4), 617-633.
[http://dx.doi.org/10.1111/j.1469-8137.1994.tb02968.x] [PMID: 33874382]
[24]
Jones, T.H.; Blum, M.S.; Robertson, H.G. Novel dialkylpiperidines in the venom of the ant Monomorium delagoense. J. Nat. Prod., 1990, 53(2), 429-435.
[http://dx.doi.org/10.1021/np50068a022] [PMID: 2380716]
[25]
Eisner, T.; Goetz, M.; Aneshansley, D.; Ferstandig-Arnold, G.; Meinwald, J. Defensive alkaloid in blood of Mexican bean beetle (Epilachna varivestis). Experientia, 1986, 42(2), 204-207.
[http://dx.doi.org/10.1007/BF01952471] [PMID: 3753941]
[26]
Shtykova, L.; Masuda, M.; Eriksson, C.; Sjödin, K.; Marling, E.; Schlyter, F.; Nydén, M. Latex coatings containing antifeedants: Formulation, characterization, and application for protection of conifer seedlings against pine weevil feeding. Prog. Org. Coat., 2008, 63, 160-166.
[http://dx.doi.org/10.1016/j.porgcoat.2008.05.006]
[27]
Gerson, E.A.; Kelsey, R.G. Piperidine alkaloids in sitka spruce with varying levels of resistance to white pine weevil (Coleoptera: Curculionidae). J. Econ. Entomol., 2002, 95(3), 608-613.
[http://dx.doi.org/10.1603/0022-0493-95.3.608] [PMID: 12076008]
[28]
Schiebe, C.; Hammerbacher, A.; Birgersson, G.; Witzell, J.; Brodelius, P.E.; Gershenzon, J.; Hansson, B.S.; Krokene, P.; Schlyter, F. Inducibility of chemical defenses in Norway spruce bark is correlated with unsuccessful mass attacks by the spruce bark beetle. Oecologia, 2012, 170(1), 183-198.
[http://dx.doi.org/10.1007/s00442-012-2298-8] [PMID: 22422313]
[29]
Funaya, N.; Haginaka, J. Matrine- and oxymatrine-imprinted monodisperse polymers prepared by precipitation polymerization and their applications for the selective extraction of matrine-type alkaloids from Sophora flavescens Aiton. J. Chromatogr. A, 2012, 1248(1248), 18-23.
[http://dx.doi.org/10.1016/j.chroma.2012.05.081] [PMID: 22695694]
[30]
Wei, R.; Cao, J.; Yao, S. Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and PINK1/Parkin pathways. Cell Stress Chaperones, 2018, 23(6), 1295-1309.
[http://dx.doi.org/10.1007/s12192-018-0937-7] [PMID: 30209783]
[31]
Cao, J.; Wei, R.; Yao, S. Matrine has pro-apoptotic effects on liver cancer by triggering mitochondrial fission and activating Mst1-JNK signalling pathways. J. Physiol. Sci., 2019, 69(2), 185-198.
[http://dx.doi.org/10.1007/s12576-018-0634-4] [PMID: 30155612]
[32]
Zhou, N.; Li, J.; Li, T.; Chen, G.; Zhang, Z.; Si, Z. Matrine induced apoptosis in Hep3B cells via the inhibition of MDM2. Mol. Med. Rep., 2017, 15(1), 442-450.
[http://dx.doi.org/10.3892/mmr.2016.5999] [PMID: 27959389]
[33]
Arena, G.; Riscal, R.; Linares, L.K.; Le Cam, L. MDM2 controls gene expression independently of p53 in both normal and cancer cells. Cell Death Differ., 2018, 25(9), 1533-1535.
[http://dx.doi.org/10.1038/s41418-018-0156-x] [PMID: 30038384]
[34]
Ikan, R. Natural products: A laboratory guide; Academic Press, 1991.
[35]
Ladenburg, A. Versuche Zur Synthese Des Coniin. Ber. Dtsch. Chem. Ges., 1886, 19, 439-441.
[http://dx.doi.org/10.1002/cber.188601901108]
[36]
Funayama, S.; Cordell, G.A. Alkaloids derived from phenylalanine and tyrosine; Elsevier, 2014.
[37]
Felpin, F-X.; Lebreton, J. A highly stereoselective asymmetric synthesis of (-)-lobeline and (-)-sedamine. J. Org. Chem., 2002, 67(26), 9192-9199.
[http://dx.doi.org/10.1021/jo020501y] [PMID: 12492320]
[38]
Raji Reddy, C.; Latha, B.; Warudikar, K.; Singarapu, K.K. Total synthesis of a piperidine alkaloid, microcosamine A. Org. Biomol. Chem., 2016, 14(1), 251-258.
[http://dx.doi.org/10.1039/C5OB02085A] [PMID: 26565783]
[39]
Felpin, F-X.; Girard, S.; Vo-Thanh, G.; Robins, R.J.; Villiéras, J.; Lebreton, J. Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco. J. Org. Chem., 2001, 66(19), 6305-6312.
[http://dx.doi.org/10.1021/jo010386b] [PMID: 11559179]
[40]
Srivastava, N.; Macha, L.; Ha, H.J. Stereoselective synthesis of 2,6-disubstituted piperidine alkaloids. Org. Biomol. Chem., 2020, 18(29), 5493-5512.
[http://dx.doi.org/10.1039/D0OB00918K] [PMID: 32478370]
[41]
Gerson, E.A.; Kelsey, R.G. Piperidine alkaloids in nitrogen fertilized Pinus ponderosa. J. Chem. Ecol., 1999, 25, 2027-2039.
[http://dx.doi.org/10.1023/A:1021080605332]
[42]
Stamp, N. Out of the quagmire of plant defense hypotheses. Q. Rev. Biol., 2003, 78(1), 23-55.
[http://dx.doi.org/10.1086/367580] [PMID: 12661508]
[43]
Wang, X-Q.; Tank, D.C.; Sang, T. Phylogeny and divergence times in Pinaceae: evidence from three genomes. Mol. Biol. Evol., 2000, 17(5), 773-781.
[http://dx.doi.org/10.1093/oxfordjournals.molbev.a026356] [PMID: 10779538]
[44]
Virjamo, V.; Julkunen-Tiitto, R.; Henttonen, H.; Hiltunen, E.; Karjalainen, R.; Korhonen, J.; Huitu, O. Differences in vole preference, secondary chemistry and nutrient levels between naturally regenerated and planted Norway spruce seedlings. J. Chem. Ecol., 2013, 39(10), 1322-1334.
[http://dx.doi.org/10.1007/s10886-013-0352-6] [PMID: 24105602]
[45]
Damodar, K.; Jun, J. An expeditious stereoselective synthesis of (−) ‐pinidinone from ethyl acetoacetate. Bull. Korean Chem. Soc., 2016, 37, 571-575.
[http://dx.doi.org/10.1002/bkcs.10728]
[46]
El-Ishaq, A.; Alshawsh, M.A.; Mun, K-S.; Chik, Z. Phytochemical screening and anti-implantation activity of Asparagus africanus root extract in female sprague-dawley rats. Rev. Bras. Farmacogn., 2019, 29, 621-630.
[http://dx.doi.org/10.1016/j.bjp.2019.06.003]
[47]
Lahtinen, B.J.O. Development and evaluation of selective melanotropins of cyclized structures, and small molecule derivatives of piperine for melanoma cell death. BS desertation, 2016.
[48]
Aadesariya, M.K.; Ram, V.R.; Dave, P.N. Investigation of phytochemicals in methanolic leaves extracts of Abutilon pannosum and grewia tenax by Q-TOF LC/MS. Prog. Chem. Biochem. Res., 2019, 2, 13-19.
[http://dx.doi.org/10.33945/SAMI/PCBR.2019.2.1319]
[49]
Robertson, G.W.; Shepherd, T.; Griffiths, D.W. The use of gas chromatography-mass. Spectrometry in the study of plant and insect defence compounds; Scottish Crop Res; Inst., 1999, p. 125.
[50]
Daly, J.W.; Karle, I.; Myers, C.W.; Tokuyama, T.; Waters, J.A.; Witkop, B. Histrionicotoxins: roentgen-ray analysis of the novel allenic and acetylenie spiroalkaloids isolated from a Colombian frog, Dendrobates histrionicus. Proc. Natl. Acad. Sci. USA, 1971, 68(8), 1870-1875.
[http://dx.doi.org/10.1073/pnas.68.8.1870] [PMID: 5288773]
[51]
Arimura, G.; Maffei, M. Plant specialized metabolism: Genomics, biochemistry, and biological functions; CRC press, 2016.
[http://dx.doi.org/10.1201/9781315370453]
[52]
Ali, B.M.; Boothapandi, M.; Sultan Nasar, A. Nitric oxide, DPPH and hydrogen peroxide radical scavenging activity of TEMPO terminated polyurethane dendrimers: Data supporting antioxidant activity of radical dendrimers. Data Brief, 2019, 28, 104972.
[http://dx.doi.org/10.1016/j.dib.2019.104972] [PMID: 31890810]
[53]
Goligorsky, M.S. Pathogenesis of endothelial cell dysfunction in chronic kidney disease: a retrospective and what the future may hold. Kidney Res. Clin. Pract., 2015, 34(2), 76-82.
[http://dx.doi.org/10.1016/j.krcp.2015.05.003] [PMID: 26484026]
[54]
de Freitas, R.M.; Silva, F. de O.; Silva, M.G. de V.; Feng, D. Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine. Rev. Bras. Farmacogn., 2011, 21, 437-443.
[http://dx.doi.org/10.1590/S0102-695X2011005000043]
[55]
Dalmia, A.; Marmor, B.; Shelton, C.T. Workflow for screening and quantification of the samhsa (nida) panel in serum using UHPLC-TOF; Perkin Almer, 2014.
[56]
Khetrapal, M.; Vodwal, L. Journal homepage, Available from:http://www.journalijar.com
[57]
Jeong, W.T.; Lim, H. Bin. Determination of isoquinoline alkaloids by UPLC-ESI-Q-TOF MS: Application to chelidonium majus L. Anal. Sci. Technol., 2017, 30, 379-389.
[58]
Wu, X.; Li, J.; Li, Z.; Liu, D.; Lu, S.; Liu, K.; Duan, H.; Luo, Y. Protective effect of tetrandrine on sodium taurocholate-induced severe acute pancreatitis. Evidence-Based Complement. Altern. Med.,, 2015, 129103.
[59]
RK.M.;, Begum,; S.;, Begum, A. Antioxidant potential of piperidine containing compounds-a short review. Atherosclerosis, 2018, 10, 12.
[60]
Liu, C.; Yang, S.; Wang, K.; Bao, X.; Liu, Y.; Zhou, S.; Liu, H.; Qiu, Y.; Wang, T.; Yu, H. Alkaloids from traditional chinese medicine against hepatocellular carcinoma. Biomed & Pharma, 2019, 120, 109543.
[http://dx.doi.org/10.1016/j.biopha.2019.109543] [PMID: 31655311]
[61]
Lin, C-H.; Chen, Y-M.; Lane, H-Y. Novel treatment for the most resistant Schizophrenia: Dual activation of NMDA receptor and antioxidant. Curr. Drug Targets, 2020, 21(6), 610-615.
[http://dx.doi.org/10.2174/1389450120666191011163539] [PMID: 31660823]
[62]
Ferreira, R.C.; Batista, T.M.; Duarte, S.S.; Silva, D.K.F.; Lisboa, T.M.H.; Cavalcanti, R.F.P.; Leite, F.C.; Mangueira, V.M.; Sousa, T.K.G.; Abrantes, R.A.; Trindade, E.O.D.; Athayde-Filho, P.F.; Brandão, M.C.R.; Medeiros, K.C.P.; Farias, D.F.; Sobral, M.V. A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions. Biomed. Pharmacother., 2020, 128, 110247.
[http://dx.doi.org/10.1016/j.biopha.2020.110247] [PMID: 32450524]
[63]
Zhang, B.; Wang, X.; Deng, J.; Zheng, H.; Liu, W.; Chen, S.; Tian, J.; Wang, F. p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma. Cancer Lett., 2019, 459, 50-58.
[http://dx.doi.org/10.1016/j.canlet.2019.05.042] [PMID: 31163195]
[64]
Yu, B.; Yuan, B.; Li, J.; Kiyomi, A.; Kikuchi, H.; Hayashi, H.; Hu, X.; Okazaki, M.; Sugiura, M.; Hirano, T.; Fan, Y.; Pei, X.; Takagi, N. JNK and autophagy independently contributed to cytotoxicity of arsenite combined with Tetrandrine via modulating cell cycle progression in human breast cancer cells. Front. Pharmacol., 2020, 11, 1087.
[http://dx.doi.org/10.3389/fphar.2020.01087] [PMID: 32765280]
[65]
Fyhrquist, P.; Virjamo, V.; Hiltunen, E.; Julkunen-Tiitto, R. Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity. Fitoterapia, 2017, 117, 138-146.
[http://dx.doi.org/10.1016/j.fitote.2017.01.011] [PMID: 28163074]
[66]
Thirunarayanan, G.; Lakshmanan, K. Bioactive 3-methyl-2, 6-diarylpiperidin-4-one, oxime and its copper (II) complex. World Sci. News, 2019, 123, 124-140.
[67]
Haider, S.; Saify, Z.S.; Begam, N.; Ashraf, S.; Zareen, T.; Saeed, S.M.G. Emerging phaaceutical applications of piperidine, pyrrolidine and it’s derivaties. World J. Pharm. Res., 2014, 3(7), 2277-7105.
[68]
Pivatto, M.; Baccini, L.R.; Sharma, A.; Nakabashi, M.; Danuello, A.; Júnior, C.V.; Garcia, C.R.S.; Bolzani, V.S.J. the beginning: global responsibility in healthcare-with a focus on tropical disease. Braz. Chem. Soc., 2014, 25(10), 1900-1906.
[69]
Chen, Q.B.; Gao, J.; Zou, G.A.; Xin, X.L.; Aisa, H.A. Piperidine alkaloids with diverse skeletons from Anacyclus pyrethrum. J. Nat. Prod., 2018, 81(6), 1474-1482.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00239] [PMID: 29775308]
[70]
Ojima, I.; Iula, D. New approaches to the syntheses of piperidine, izidine, and quinazoline alkaloids by means of transition metal catalyzedcarbonylations. ChemInform, 2000, 31.

Rights & Permissions Print Cite
Article Metrics
43
2
© 2024 Bentham Science Publishers | Privacy Policy