Piperdardine

Molecular docking and molecular dynamics simulation approach to screen natural compounds for inhibition of Xanthomonas oryzae pv. Oryzae by targeting peptide deformylase.[Pubmed:31965918]

J Biomol Struct Dyn. 2021 Feb;39(3):823-840.

Xanthomonas oryzae pv. Oryzae (Xoo) causes bacterial leaf blight (BLB) of rice which results in a huge loss in production. Many chemicals are used to control BLB disease. However, these chemicals are toxic to the environments, animals and human beings. Thus, there is a demand to discover potential and safe natural pesticides to manage BLB disease successfully. Therefore, we screened a library of phytochemicals of different plants having antibacterial activity by targeting Peptide Deformylase (PDF) of Xoo using in silico techniques. A library of 318 phytochemicals was prepared and subjected to rigid and flexible molecular docking against PDF followed by molecular dynamics simulation and free energy analysis of protein-ligand complexes. The results of virtual screening showed that 14 compounds from different plants have good binding energy as compare to reference molecule (3 R)-2,3-dihydro[1,3] thiazolo [3,2 a]benzimidazol-3-ol) (-7.7 kcal mol(-1)). Out of 14 hit compounds, eight compounds that were selected based on binding energy were analyzed by Molecular dynamic (MD) simulation. Analysis of MD simulation revealed that eight compounds namely; Bisdemethoxycurcumin, Rosmarinic acid, Piperanine, Dihydropiperlonguminine, Piperdardine, Dihydrocurcumin and Lonhumosides B achieved good stability during the 80 ns MD simulation at 300 K in term of the RMSD. Further, we calculated RMSF, RG, SASA, and interaction energy after 40 ns due to showing the stability of complexes. From our results, we conclude that these natural compounds could inhibit Xoo by targeting PDF receptor and can be used as potential bactericidal candidates against BLB disease of rice against Xoo and other bacteria. Communicated by Ramaswamy H. Sarma.

Sensory active piperine analogues from Macropiper excelsum and their effects on intestinal nutrient uptake in Caco-2 cells.[Pubmed:28065397]

Phytochemistry. 2017 Mar;135:181-190.

The phytochemical profile of Macropiper excelsum (G.Forst.) Miq. subsp. excelsum (Piperaceae), a shrub which is widespread in New Zealand, was investigated by LC-MS-guided isolation and characterization via HR-ESI-TOF-MS and NMR spectroscopy. The isolated compounds were sensorily evaluated to identify their contribution to the overall taste of the crude extract with sweet, bitter, herbal and trigeminal impressions. Besides the known non-volatile Macropiper compounds, the lignans (+)-diayangambin and (+)-excelsin, four further excelsin isomers, (+)-diasesartemin, (+)-sesartemin, (+)-episesartemin A and B were newly characterized. Moreover, piperine and a number of piperine analogues as well as trans-pellitorine and two homologues, kalecide and (2E,4E)-tetradecadienoic acid N-isobutyl amide were identified in M. excelsum, some of them for the first time. Methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate was identified and characterized for the first time in nature. Sensory analysis of the pure amides indicated that they contributed to the known chemesthetic effects of Macropiper leaves and fruits. Since the pungent piperine has been shown to affect glucose and fatty acid metabolism in vivo in previous studies, piperine itself and four of the isolated compounds, Piperdardine, chingchengenamide A, dihydropiperlonguminine, and methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate, were investigated regarding their effects on glucose and fatty acid uptake by enterocyte-like Caco-2 cells, in concentrations ranging from 0.1 to 100 muM. Piperdardine showed the most pronounced effect, with glucose uptake increased by 83 +/- 18% at 100 muM compared to non-treated control cells. An amide group seems to be advantageous for glucose uptake stimulation, but not necessarily for fatty acid uptake-stimulating effects of piperine-related compounds.

Cytotoxic Amides from Fruits of Kawakawa, Macropiper excelsum.[Pubmed:26039266]

Planta Med. 2015 Aug;81(12-13):1163-8.

Cytotoxic amides have been isolated from the fruits of the endemic New Zealand medicinal plant kawakawa, Macropiper excelsum (Piperaceae). The main amide was piperchabamide A and this is the first report of this rare compound outside the genus Piper. Eleven other amides were purified including two new compounds with the unusual 3,4-dihydro-1(2H)-pyridinyl group. The new compounds were fully characterized by 2D NMR spectroscopy, which showed a slow exchange between two rotamers about the amide bond, and they were chemically synthesized. In view of the antitumor activity of the related piperlongumine, all of these amides plus four synthetic analogs were tested for cytotoxicity. The most active was the piperine homolog Piperdardine, with an IC50 of 14 microM against HT 29 colon cancer cells.

[Alkaloids and lignans from stems of Piper betle].[Pubmed:21137339]

Zhongguo Zhong Yao Za Zhi. 2010 Sep;35(17):2285-8.

Alkaloids and lignans from the stems of Piper betle were studied. Compounds were isolated and purified by repeated silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography and preparative thin layer chromatography. The structures were elucidated on the basis of spectral analysis. From the ethyl acetate soluble fractions of the 70% acetone extract, ten compounds were isolated and identified as piperine (1), pellitorine (2), N-isobutyl-2E,4E-dodecadienamide (3), dehydropipernonaline (4), Piperdardine (5), piperolein-B (6), guineensine (7), (2E,4E)-N-isobutyl-7-(3',4'-methylenedioxyphenyl)-2,4-heptadienamide (8), syringaresinol-O-beta-D-glucopyranoside (9),pinoresinol (10). All Compounds were isolated from the plant for the first time, and compounds 9 and 10 were isolated firstly from the genus.

Analysis by HPLC and LC/MS of pungent piperamides in commercial black, white, green, and red whole and ground peppercorns.[Pubmed:18386929]

J Agric Food Chem. 2008 May 14;56(9):3028-36.

Pepper plants accumulate pungent bioactive alkaloids called piperamides. To facilitate studies in this area, high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry methods were developed and used to measure the following piperamides in 10 commercial whole (peppercorns) and in 10 ground, black, white, green, and red peppers: piperanine, Piperdardine, piperine, piperlonguminine, and piperettine. Structural identification of individual compounds in extracts was performed by associating the HPLC peak of each compound with the corresponding mass spectrum. The piperanine content of the peppers (in mg/g piperine equivalents) ranged from 0.3 for the ground white pepper to 1.4 in black peppercorns. The corresponding range for Piperdardine was from 0.0 for seven samples to 1.8 in black peppercorns; for four isomeric piperines, from 0.7 for red to 129 in green peppercorns; for piperlonguminine, from 0.0 in red peppercorns to 1.0 in black peppercorns; and for piperyline, from 0.9 in ground black pepper to 5.9 for red peppercorn. Four well-separated stereoisomeric forms of piperettine with the same molecular weight were present in 19 peppers. The sums of the piperamides ranged from 6.6 for red to 153 for green peppercorns. In contrast to large differences in absolute concentrations among the peppers, the ratios of piperines to total piperamide were quite narrow, ranging from 0.76 for black to 0.90 for white peppercorns, with an average value of 0.84 +/- 0.04 ( n = 19). Thus, on average, the total piperamide content of the peppers consists of 84% piperines and 16% other piperamides. These results demonstrate the utility of the described extraction and analytical methods used to determine the wide-ranging individual and total piperamide contents of widely consumed peppers.

New optimized piperamide analogues with potent in vivo hypotensive properties.[Pubmed:15567289]

Eur J Pharm Sci. 2004 Dec;23(4-5):363-9.

We describe herein the structural optimization of new piperamide analogues, designed from two natural prototypes, piperine 1 and Piperdardine 2, obtained from Piper tuberculatum Jacq. (Piperaceae). Molecular modeling studies using semiempirical AM1 method were made in order to establish rational modifications to optimize them by molecular simplification. The targeted compounds (10) and (11) were respectively obtained using benzaldehyde (12) and para-anisaldehyde (13) as starting materials. 1H NMR spectra showed that the target compounds were diastereoselectively obtained as the (E)-isomer, the same geometry of the natural prototypes. These new synthetic amides presented significant hypotensive effects in cardiovascular essays using in vivo methodologies. Compound 11 (N-[5-(4'-methoxyphenyl)-2(E)-pentenoyl]thiomorpholine) showed a potency 10,000 times greater than its prototype 5, evidencing an optimization of the molecular architecture for this class of hypotensive drug candidates.

Constituents of Chinese Piper species and their inhibitory activity on prostaglandin and leukotriene biosynthesis in vitro.[Pubmed:11297843]

J Ethnopharmacol. 2001 May;75(2-3):133-9.

The n-hexane extracts of 19 Piper species, predominantly from China, were screened for their 5-lipoxygenase (5-LOX) and cyclooxygenase-1 (COX-1) inhibitory potential. Many of them showed considerable inhibitory activity against at least one of these two key enzymes of the arachidonic acid metabolism, especially against COX-1. The best results in inhibiting the formation of leukotrienes were obtained with the extract of Piper kadsura. In the terms of prostaglandin synthesis inhibition, the extract of Piper boehmeriifolium var. tonkinense was found to have the strongest activity. Furthermore, an analytical investigation by means of TLC, HPLC-DAD and GC-MS resulted in the identification of 20 constituents. Most of them were amides with an interesting variety of amine moieties. Among them were pellitorine, and four higher homologues, piperlonguminine, dihydropiperlonguminine, futoamide, chingchengenamide, the retrofractamides A, B and D, guineensine, brachystamide B, piperanine, piperine, Piperdardine, sarmentine, pipataline and benzylbenzoate. In 96 cases, these constituents were new for the particular plant.