ABSTRACT
19 compounds, including seven previously undescribed alkaloids ((-)-macleayin K (1), (+)-macleayin K (2), macleayin M (3), macleayin N (4), macleayin L (5), macleayin O (6), oxohydrastinine A (7), one new natural product (8), and 11 known compounds, were isolated from the fruit pods of Macleaya microcarpa. Their structures were defined based on NMR, HRESIMS, and electronic circular dichroism (ECD) data. A network pharmacology approach combined with molecular docking and in vitro validation was performed to determine the bioactivity, key targets of the 19 compounds against breast cancer (BC) and cervical cancer (CC). EGFR and PIK3CA could become potential therapeutic targets based a network pharmacology. Moreover, molecular docking suggested that the 19 compounds combined well with EGFR and PIK3CA, respectively. Their cytotoxicity of selected compounds was tested against the MCF-7 and HeLa cells, and the preliminary structure-activity relationship is discussed. Compounds 1 (IC50: 6.00 µM) and 2 (IC50: 6.82 µM) exhibited strong inhibitory activity against the HeLa cells and are worthy of further study.
Subject(s)
Alkaloids , Antineoplastic Agents , Papaveraceae , Humans , Fruit , HeLa Cells , Molecular Docking Simulation , Molecular Structure , Papaveraceae/chemistry , ErbB ReceptorsABSTRACT
Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline alkaloids, thalicultratines A-K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, and five known ones were isolated from the roots of Thalictrum cultratum. Their structures were defined on the basis of NMR and HRESIMS data. The antiproliferative activities of compounds 1-17 were evaluated against human leukemia HL-60 and prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity against selected cancer cells. Preliminary SARs are discussed. The most active new compound (3), with an IC50 value of 1.06 µM against HL-60 cells, was selected for mechanism of action studies. The results revealed that compound 3 induced apoptosis and arrested the HL-60 cell cycle at the S phase with the loss of mitochondria membrane potential. The nuclear morphological Hoechst 33258 staining assay was also carried out, and the results confirmed apoptosis.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Aporphines/isolation & purification , Aporphines/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Plant Roots/chemistry , Thalictrum/chemistry , Alkaloids/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Aporphines/chemistry , Berberine Alkaloids , Drugs, Chinese Herbal/chemistry , HL-60 Cells , Humans , Inhibitory Concentration 50 , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity RelationshipABSTRACT
Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones, flemiphilippinones B (1) and C (2), and one new pterocarpoid, demethylwedelolactone-11-methyl ether (3), together with 12 known compounds (4-15). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI50 value of 14.12µM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI50 values of 1.91 and 2.58µM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway.
Subject(s)
Chalcones/chemistry , Fabaceae/chemistry , Plant Roots/chemistry , Pterocarpans/chemistry , Apoptosis , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation/drug effects , Chalcones/isolation & purification , Humans , Molecular Structure , Pterocarpans/isolation & purificationABSTRACT
Three new phenylnaphthalene-type lignans, vitexnegheteroins E-G (1-3), and a new polyoxygenated ursane-type triterpene, vitexnegheteroin H (9), were isolated from the seeds of Vitex negundo var. heterophylla, together with ten known compounds. Their structures were established on the basis of extensive 1D and 2D NMR experiments, as well as their mass spectroscopic data. The absolute configurations of compounds 1 and 2 were determined by comparing their experimental ECD spectra with that calculated by the time-dependent density functional theory (TDDFT) method. The isolates were evaluated for their cytotoxicities against three human cancer cell lines, inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells, and antioxidant activities for ABTS radical scavenging.
Subject(s)
Lignans/chemistry , Triterpenes/chemistry , Vitex/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Humans , Lignans/isolation & purification , Mice , Microglia/drug effects , Molecular Structure , Nitric Oxide/metabolism , Triterpenes/isolation & purificationABSTRACT
Two pairs of enantiomeric alkaloid dimers, (±)-macleayins A (1) and B (2), representing a novel dimerization pattern of two different types of alkaloids via a C-C σ-bond, were isolated from the aerial parts of Macleaya cordata. The enantiomeric separation was achieved by chiral chromatography. Their structures and stereochemistry were determined by the analysis of extensive spectroscopic data, electronic circular dichroism calculation, and single-crystal X-ray diffraction data. (-)-Macleayin A exhibits modest cytotoxic activity against HL-60 cell line with the IC50 value of 3.51 µM.
