Showing papers on "Piperlonguminine published in 2021"

Novel Phenylmethylenecyclohexenone Derivatives as Potent TrxR Inhibitors Display High Antiproliferative Activity and Induce ROS, Apoptosis, and DNA Damage

Abstract: The natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL's potency, we designed and synthesized a series of 17 novel phenylmethylenecyclohexenone derivatives and evaluated their pharmacological properties. Most of them exerted antiproliferative activities against four cancer cell lines with IC50 values lower than PL. Among these, compound 10 e not only showed good water solubility and exerted the most potent antiproliferative activity against HGC27 cells (IC50 =0.76 μM), which was 10-fold lower than PL (IC50 =7.53 μM), but also exhibited lower cytotoxicity in human normal gastric epithelial cells GES-1 compared with HGC27 cells. Mechanistically, compound 10 e inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, and diminished mitochondrial transmembrane potential (MTP) in HGC27 cells. Furthermore, 10 e also induced G2 /M cell-cycle arrest, and triggered cancer cell apoptosis through the regulation of apoptotic proteins. Finally, 10 e promoted DNA damage in HGC27 cells via the activation of the H2AX(S139ph) and p53 signaling. In conclusion, 10 e, with prominent tumor selectivity and water solubility, could be a promising candidate for the treatment of cancer and, as such, warrants further investigation.

Efficient separation of N-Alkylamides from Piper longum L. using off-line two-dimensional coupled with gradient high-speed counter-current chromatography

Abstract: Piper longum L. (Piperaceae) is famous for flavoring food and treatment purposes. N-Alkylamides (NAAs) are the most common secondary metabolites found in Piper species with broad spectrum of biological properties. Because of the similar structures and lower polarities, it is difficult to separate NAAs by traditional chromatographic methods. Herein, an efficient off-line two-dimensional coupled with gradient high-speed counter-current chromatography (HSCCC) method is reported for preparative separation of N-alkylamides from P. longum. The HSCCC solvent system with n-hexane/ethyl acetate/methanol/water (5:4:5:4, v/v) was used for the first dimensional separation. Two pure compounds i.e. piperlonguminine (1) and piperine (2) were successfully separated, coupled with an enriched trace ingredient. Furthermore, the enriched ingredient was used for the second dimensional separation with a gradient HSCCC mode by adjustment of the mobile phase with more enhanced elution ability. Eight minor compounds were successfully separated including retrofractamide A (3), retrofractamide C (4), dehydropipernonaline (5), pipernonaline (6), piperundecalidine (7), guineesine (8), brachystamide B (9), and (2E,4E,12Z)-N-isobutyl-2,4,12- octadecatrienamide (10). The structures of the isolated pure compounds were characterized by ESI-MS, 1H, and 13C NMR spectral analysis.

Molecular docking analysis of vascular endothelial growth factor receptor with bioactive molecules from Piper longum as potential anti-cancer agents.

Abstract: It is known that vascular endothelial growth factor receptor (VGFR) is linked with cancer. Therefore, it is of interest to document the molecular binding features of bioactive molecules from Piper longum as potential anti-cancer agents with VGFR2 for further consideration. Thus, we document the binding features of four compounds (sesamin, fargesin, longamide and piperlonguminine) with VGFR2 for further consideration in drug discovery.

Amide alkaloids from Piper guineense and its crude extract as protectants against Sitophilus zeamais

Abstract: The edible plant, Piper guineense Schum and Thonn, belongs to the family Piperaceae and possesses insecticidal properties against stored product insects, but information on isolation and use of its amide alkaloids for the control of insect pests is scanty. Therefore, amide alkaloids from P. guineense fruits as well as its crude extract were investigated as protectant against Sitophilus zeamais Motschulschy (Coleoptera: Curculionidae), a cosmopolitan insect pest. Chemical analysis of P. guineense was done using chromatographic techniques and amide alkaloids were identified using liquid chromatography–quadrupole time of flight-mass spectrometry (LC-QToF-MS). The compounds were assayed on five pairs of two-day-old S. zeamais, feeding with the maize variety, TZPB-SR-W. All parameters, including mortality and oviposition by female S. zeamais, repellent effect of the compounds and their effects on maize seed germination, were evaluated relative to the synthetic chemical, pirimiphos-methyl and ethanol, as positive and negative controls, respectively. The six compounds identified were dihydrowisanine (1.01%), guineensine (0.22%), piperine (6.64%), piperlonguminine (0.25%), propiverine (0.16%) and trichostachine (3.80%). Guineensine and piperine caused the highest mortalities (97.5% and 82.5%, respectively) of S. zeamais, which were not significantly different from the mortality (100%) caused by pirimiphos-methyl. In addition, piperine treatment significantly reduced oviposition (0.75 per grain) when compared to ethanol-treated grains (5.00 per grain). There were no significant differences in per cent germination between maize seeds treated with the amide compounds and those included in the control groups (positive and negative controls). Amide alkaloids from P. guineense offer a useful source of biopesticide material for controlling S. zeamais.