ABSTRACT
Phytochemical studies of the stems and leaves of Stephania dielsiana Y.C.Wu yielded two new aporphine alkaloids (1 and 5), along with six known alkaloids (2-4 and 6-8). Their structures were characterised based on analyses of spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS). The cytotoxic activities of the isolated compounds against a small panel of tumour cell lines were assessed by MTS assay. Interestingly, compound 2 exhibited particularly strong cytotoxic activities against HepG2, MCF7 and OVCAR8 cancer cell lines, with IC50 values of 3.20 ± 0.18, 3.10 ± 0.06 and 3.40 ± 0.007 µM, respectively. Furthermore, molecular docking simulations were carried out to explore the interactions and binding mechanisms of the most active compound (compound 2) with proteins. Our results contribute to understanding the secondary metabolites produced by S. dielsiana and provide a scientific rationale for further investigations of cytotoxicity of this valuable medicinal plant.
Subject(s)
Alkaloids , Antineoplastic Agents, Phytogenic , Aporphines , Molecular Docking Simulation , Plant Leaves , Plant Stems , Stephania , Aporphines/chemistry , Aporphines/pharmacology , Humans , Plant Leaves/chemistry , Plant Stems/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Stephania/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Molecular Structure , Cell Line, Tumor , Hep G2 Cells , MCF-7 Cells , Drug Screening Assays, Antitumor , Magnetic Resonance Spectroscopy , Plants, Medicinal/chemistryABSTRACT
Three new amide alkaloids, piperlongumamides D-F (14, 19, and 32); a new piperic ester, piperlongumester A (45); and two new natural compounds, methyl (2E,4Z)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoate (46) and trans-piperolein B ester (47), along with 41 known compounds were isolated from the fruits of Piper longum L. Their structures were identified by analyzing spectroscopic data, including mass spectrometry, 1D, and 2D NMR data. The anti-inflammatory and cytotoxic activities of all isolated compounds (1-47) were evaluated. Compounds 3, 6, and 19 inhibited nitric oxide production with IC50 values of 16.1 ± 0.94, 14.5 ± 0.57, and 27.3 ± 1.11 µM, respectively, whereas compound 1 exhibited strong cytotoxic activity toward three ovarian cancer cell lines A2780, TOV-112D, and SK-OV3, with IC50 values of 6.7 ± 0.77, 5.8 ± 0.29, and 48.3 ± 0.40 µM, respectively. Molecular docking simulations were performed to identify the interaction and binding mechanisms of these active metabolites with proteins related to inflammation and cancer.
Subject(s)
Alkaloids , Antineoplastic Agents , Ovarian Neoplasms , Piper , Alkaloids/chemistry , Amides/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Esters/pharmacology , Female , Fruit/chemistry , Humans , Molecular Docking Simulation , Molecular Structure , Ovarian Neoplasms/drug therapy , Piper/chemistryABSTRACT
Chromatography of the ethanol extract of the medicinal fruit Stauntonia hexaphylla resulted in the purification of 26 compounds (1-26), including two undescribed triterpene saponins 1 and 2 (hexaphylosides A and B). Their structures were confirmed by spectroscopic data, including IR, HR QTOF MS, 1H, 13C NMR, COSY, HMQC, HMBC, and TOCSY, and HPLC sugar analysis after acid hydrolysis. The anti-inflammatory effects of the high-purity constituents (1-26) on lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells were investigated by screening nitric oxide production. The NO inhibitory activity of compounds 6 and 10 with the IC50 values of 1.33 and 1.10⯵M, respectively. The structure-activity relationships (SAR) of the isolated compounds were also analyzed. Furthermore, compounds 6 and 10 inhibited the protein expression inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 via Western blotting analysis. This showed that compounds 6 and 10 contributed to the anti-inflammatory effects of S. hexaphylla fruit, which could be developed as a natural nutraceutical and functional food ingredient.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/isolation & purification , Cyclooxygenase 2 Inhibitors/pharmacology , Fruit/chemistry , Mice , Molecular Structure , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , RAW 264.7 Cells , Ranunculales/chemistry , Saponins/chemistry , Saponins/isolation & purification , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purificationABSTRACT
Eight compounds were isolated from the leaves of Clerodendrum inerme, including one new rearranged abietane diterpene, crolerodendrum B (1). Their structures were determined by means of spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance (1-D and 2-DNMR), high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and circular dichroism (CD). The DPPH radical scavenging and cytotoxic activities of isolated compounds against MCF7 (breast), HCT116 (colon) and B16F10 (melanoma) cancer cell lines were evaluated. Compounds 1, 3 and 4 exhibited strong DPPH radical-scavenging effects (ED50 values of 17.6 ± 2.1, 10.1 ± 0.8 and 11.3 ± 0.3 µM, respectively) and 4 showed strong cytotoxicity against the HCT116 cell line (IC50 = 3.46 ± 0.01 µM).
