- Amides from Piper capense with CNS activity - A preliminary SAR analysis
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Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.
- Pedersen, Mikael E.,Metzler, Bjorn,Stafford, Gary I.,Van Staden, Johannes,Jaeger, Anna K.,Rasmussen, Hasse B.
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- Regioselective reduction of the α, β - double bond of some naturally occurring dienamides using NaBH4/I2 system
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The regioselective reduction of the α, β - double bond of the naturally occurring dienamides, piperine, piperlonguminine and N - isobutyl - 2E, 4E - decadienamide was achieved by using NaBH4/I2 system.
- Das, Biswanath,Kashinatham,Madhusudhan
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- Highly Selective Hydrogenation of C═C Bonds Catalyzed by a Rhodium Hydride
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Under mild conditions (room temperature, 80 psi of H2) Cp*Rh(2-(2-pyridyl)phenyl)H catalyzes the selective hydrogenation of the C═C bond in α,β-unsaturated carbonyl compounds, including natural product precursors with bulky substituents in the β position and substrates possessing an array of additional functional groups. It also catalyzes the hydrogenation of many isolated double bonds. Mechanistic studies reveal that no radical intermediates are involved, and the catalyst appears to be homogeneous, thereby affording important complementarity to existing protocols for similar hydrogenation processes.
- Gu, Yiting,Lisnyak, Vladislav G.,Norton, Jack R.,Salahi, Farbod,Snyder, Scott A.,Zhou, Zhiyao
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supporting information
p. 9657 - 9663
(2021/07/19)
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- PROCESS FOR THE PREPARATION OF PIPERINE
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The present application relates to a process for the preparation of piperine of high purity having low concentrations of isomeric impurities.
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Page/Page column 9; 15
(2019/05/02)
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- Fragmentation pattern of amides by EI and HRESI: Study of protonation sites using DFT-3LYP data
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Amides are important natural products which occur in a few plant families. Piplartine and piperine, major amides in Piper tuberculatum and P. nigrum, respectively, have shown a typical N-CO cleavage when analyzed by EI-MS or HRESI-MS. In this study several synthetic analogs of piplartine and piperine were subjected to both types of mass spectrometric analysis in order to identify structural features influencing fragmentation. Most of the amides showed an intense signal of the protonated molecule [M + H]+ when subjected to both HRESI-MS and EI-MS conditions, with a common outcome being the cleavage of the amide bond (N-CO). This results in the loss of the neutral amine or lactam and the formation of aryl acylium cations. The mechanism of N-CO bond cleavage persists in α,β-unsaturated amides because of the stability caused by extended conjugation. Computational methods determined that the protonation of the piperamides and their derivatives takes place preferentially at the amide nitrogen supporting the dominant the N-CO bond cleavage.
- Fokoue,Marques,Correia,Yamaguchi,Qu,Aires-De-Sousa,Scotti,Lopes,Kato
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p. 21407 - 21413
(2018/06/26)
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- Synthesis and inhibitory effect of piperine derivates on monoamine oxidase
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A series of piperine derivates (1-19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC 50(MAO-B) = 0.045 μM) and good selectivity (IC50(MAO-A) = 3.66 μM). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report.
- Mu, Li-Hua,Wang, Bo,Ren, Hao-Yang,Liu, Ping,Guo, Dai-Hong,Wang, Fu-Meng,Bai, Lin,Guo, Yan-Shen
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scheme or table
p. 3343 - 3348
(2012/06/29)
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- In vitro TRPV1 activity of piperine derived amides
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A series of natural and synthetic piperine amides were evaluated for activity on the human TRPV1 expressed in HEK293 cells. The agonistic effect of piperine amides was mainly dependent on the length of the carbon chain. Structural changes of double bonds and stereochemistry in the aliphatic chain of these compounds did not change their potency or efficacy, indicating that increased rigidity or planarity of the piperine structure does not affect the activity. The opening of the methylenedioxy ring or changes in the heterocyclic ring of the piperine molecule reduced or abolished activity. Furthermore, inactive compounds did not display functional antagonistic activity.
- Correa, Edwin Andrés,H?gest?tt, Edward D.,Sterner, Olov,Echeverri, Fernando,Zygmunt, Peter M.
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experimental part
p. 3299 - 3306
(2010/07/04)
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- Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors
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Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors.
- Sangwan, Payare L.,Koul, Jawahir L.,Koul, Surrinder,Reddy, Mallepally V.,Thota, Niranjan,Khan, Inshad A.,Kumar, Ashwani,Kalia, Nitin P.,Qazi, Ghulam N.
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experimental part
p. 9847 - 9857
(2009/04/11)
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- Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi
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We describe herein an evaluation of trypanocidal effects of the natural alkaloid piperine and twelve synthetic derivatives against epimastigote and amastigote forms of the protozoan parasite Trypanosoma cruzi, the causative agent of the incurable human disease, Chagas' disease. The results obtained point to piperine as a suitable template for the development of new drugs with trypanocidal activity.
- Ribeiro, Tatiana Santana,Freire-De-Lima, Leonardo,Previato, Jose Osvaldo,Mendonca-Previato, Lucia,Heise, Norton,De Lima, Marco Edilson Freire
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p. 3555 - 3558
(2007/10/03)
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- Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation
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A wide range of piperine analogues has been synthesised in order to undertake a structure-activity study of their ability to stimulate melanocyte proliferation. Results demonstrate that an aromatic ring containing at least one ether function and a carbonyl group containing side chain is essential for this activity. A number of highly active piperine analogues have been identified, for instance 1-(3,4-methylenedioxyphenyl)-penta-2E,4E-dienoic acid methyl ester (5a), 1-E,E-piperinoyl-isobutylamine (4f) and 1-(3,4- methylenedioxyphenyl)-pentanoic acid cyclohexyl amide (20). A selection of analogues has also been evaluated for their effect on melanocyte morphology and melanogenesis. The piperine analogues altered cell morphology by increasing dendrite formation leading to bi-, tri- and quadripolar cells. These same analogues were found to increase total melanin in cell cultures, although melanin content per cell was not significantly altered from control in the presence of these compounds.
- Venkatasamy, Radhakrishnan,Faas, Laura,Young, Antony R.,Raman, Amala,Hider, Robert C.
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p. 1905 - 1920
(2007/10/03)
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- GC/MS investigations of the minor constituents of Piper guineense stem
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Chemical investigations by GC/MS-analysis of stem extracts of Piper guineense resulted in the detection and identification of thirty-nine new constituents of the stem, apart from previously isolated constituents. These are isobutyl, pyrrolidyl and piperidyl amide alkaloids. Fifteen new natural products have been identified. Four of these natural products have been designated iyeremide A and B (these are pyrrolidine and piperidine analogues of pellitorine) and cycloguineense A and B, which are also piperidine analogues of cyclostachine A and B. There is a need to confirm the structures of some of these new constituents by synthesis. Apart from these amide alkaloids, many volatile oil components-monoterpenes, sesquiterpenes, terpenoids, lignans and sterols - were detected.
- Adesina,Adebayo,Adesina,Groening
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p. 622 - 627
(2007/10/03)
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- Is a nitrogen atom an important pharmacophoric element in sigma ligand binding?
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A lingering question in σ receptor ligand development is whether a nitrogen atom serves as an important pharmacophoric element in binding affinity. To address this question, we have synthesized several phenylalkylpiperidines and phenylalkylpiperazines and
- Ablordeppey, Seth Y.,Fischer, James B.,Glennon, Richard A.
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p. 2105 - 2111
(2007/10/03)
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- Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities
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Inhibitors of drug metabolism have important implications in pharmaco- toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs. (C) 2000 Elsevier Science Ltd.
- Koul, Surrinder,Koul, Jawahir L.,Taneja, Subhash C.,Dhar, Kanaya L.,Jamwal, Deshvir S.,Singh, Kuldeep,Reen, Rashmeet K.,Singh, Jaswant
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p. 251 - 268
(2007/10/03)
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- Synthesis and nematocidal activity of aralkyl- and aralkenylamides related to piperamide on second-stage larvae of Toxocara canis
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Seventy-nine aralkyl- and aralkenylamides related to piperamides were synthesized and their nematocidal activity against second-stage larvae of dog roundworm, Toxocara canis, was examined. The activity was greatly dependent on the alkyl chain length and the nature of the amine moiety, but was scarcely affected by the presence or absence of double bond(s) in the chain. The alkyl chain lengths which showed the strongest activity in a series of homologues were m=11 for the pyrrolidine amides and m=13 for the N- methylpiperazine amides. Although piperamides (3,4-methylenedioxyphenyl homologues) showed the strongest activity among the homologues tested, methoxy substituent(s) on the aromatic ring did not have much effect on the activity. However, conversion of the methoxy group to a hydroxy group greatly decreased the activity and shortened the chain length giving the strongest activity. Calculated log P values of non-phenolic aryl-piperamides fell in the range from 3.5 to 4.5, whereas those of hydroxyphenyl-piperamides were smaller, suggesting that different mechanisms are involved in the nematocidal activity of phenolic and non-phenolic compounds.
- Kiuchi, Fumiyuki,Nakamura, Norio,Saito, Makiko,Komagome, Kazue,Hiramatsu, Hirokuni,Takimoto, Noriaki,Akao, Nobuaki,Kondo, Kaoru,Tsuda, Yoshisuke
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p. 685 - 696
(2007/10/03)
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- Infrared Spectra of Conjugated Amides: Reassignment of the C=O and C=C Absorptions
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Inspections of the infrared spectra of more than twenty tertiary and secondary amides and acid-induced shift experiments clarified that, in open chain amides, the carbonyl absorption shifts to lower frequency by 10-20 cm-1 when a conjugation is introduced and that, among the plural absorptions at 1600-1700 cm-1 in conjugated amides, the lowest absorption (usually the most intense one) should be attributable to the C=O and the higher absorptions are assignable to the C=C.Keywords - conjugated amide; piperamide; IR; carbonyl absorption; acid-induced shift.
- Nakamura, Norio,Kiuchi, Fumiyuki,Tsuda, Yoshisuke
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p. 2647 - 2651
(2007/10/02)
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- Occurrence of an Alkaloid in the Seeds of Anethum sowa
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Chemical investigation of Anethum sowa seeds has led to the isolation of piperine (III), β-sitosterol and its glucoside.This is the first report on the isolation of an alkaloid from Anethum genus, and the only other source of natural occurrence of piperine besides the Piper genus.
- Jain, A. K.,Sharma, N. D.,Gupta, S. R.
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- A Convenient Reduction of Activated Olefins by Zinc-Copper Couple
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Activated olefins of the types Ph2C=CXY, R2C=CXY, PhRC=CXY, and RCH=CXY (where X and Y are electronegative substituents or one of them is a hydrogen atom) have been reduced to the corresponding saturated compounds in excellent yields by treatment with zinc-copper couple in boiling methanol.
- Sondengam, B. Lucas,Fomum, Z. Tanee,Charles, Georges,Akam, T. Mac
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p. 1219 - 1222
(2007/10/02)
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