ABSTRACT
Alpiniamides E-G, three previously unreported linear polyketide derivatives, along with two known compounds, were isolated from Streptomyces sp. QHA48, which was isolated from the saline lakes of Qinghai-Tibet Plateau. The structures of these compounds were determined through analysis of their spectroscopic data, as well as density functional theory prediction of NMR chemical shifts, application of the DP4+ algorithm and electronic circular dichroism (ECD) calculations. In a cell-based lipid-lowering assay, all five alpiniamides exhibited significant inhibition of lipid accumulation in HepG2 cells without inducing cytotoxic effects at a concentration of 27â µM.
Subject(s)
Lakes , Streptomyces , Streptomyces/chemistry , Circular Dichroism , Magnetic Resonance Spectroscopy , Lipids/pharmacology , Molecular StructureABSTRACT
A new SEK15-derived polyketide compound, strepolyketide D (1), was isolated from salt-lake-derived Streptomyces sp. DBC5, together with two known analogues (2-3). Their structures were elucidated based on spectroscopic analysis of IR, MS, 1 D and 2 D NMR. Compound 2 elicited moderate antioxidation with IC50 value of 39.26 µg/ml. The results of the study revealed that salt-lake actinomycetes of Lake Dabancheng appear to have immense potential as a source of polyketide compounds.
Subject(s)
Polyketides , Streptomyces , Streptomyces/chemistry , Lakes , Magnetic Resonance SpectroscopyABSTRACT
Two new p-methoxyphenyl-type derivatives cytchloramol (1) and cytoxazinanone (2), along with six known compounds (3-8) were identified from the chemical investigations of a saline lake actinomycete, Streptomyces sp. XZB32. The structures of the new compounds were elucidated by extensive NMR spectroscopic analysis, HRESIMS data, GIAO (gauge-including atomic orbitals) NMR, specific optical rotation (SOR) and electronic circular dichroism (ECD) calculations. Cytotoxicity evaluation of the two new compounds showed that compound 1 exhibited significant activity against HCT-116 and MDA-MB-231 human cancer cell line with IC50 values of 2.7 ± 0.07 µM and 1.54 ± 0.14 µM, respectively.
ABSTRACT
Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain of Saccharomyces cerevisiae by whole-genome sequencing of many independent isolates (n = 93) subcloned about 100 times in unstressed growth conditions. The most common alterations were point mutations and small (<100 bp) insertion/deletions (n = 1,337) and mitotic recombination events (n = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually less than 15 kb) and terminal events (mostly cross-overs) in which the LOH tract extends to the end of the chromosome. These two types of LOH events had different distributions, suggesting that they may have initiated by different mechanisms. Based on our results, we present a method of calculating the probability of an LOH event for individual SNPs located throughout the genome. We also identified several hotspots for chromosomal rearrangements (large deletions and duplications). Our results provide insights into the relative importance of different types of genetic alterations produced during vegetative growth.
Subject(s)
Chromosomes, Fungal/genetics , Mutation/genetics , Saccharomyces cerevisiae/genetics , Chromosome Mapping , Diploidy , Gene Conversion/genetics , Gene Rearrangement/genetics , Loss of Heterozygosity/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics , Saccharomyces cerevisiae/cytologyABSTRACT
Eleven new pyrimidine nucleosides (1-11) and 12 known analogues (12-23) were isolated from the marine-derived Streptomyces sp. SSA28. All of the new structures were elucidated by extensive NMR spectroscopic analysis and HRESIMS data. The absolute configurations of compound 1 were determined by X-ray diffraction. The configurations of 2-16 were investigated by ECD calculations. Compounds 11-16 showed cytotoxicity against HCT-116 human colon cancer cell lines with IC50 values from 0.39 ± 0.03 to 6.63 ± 0.47 µM.
Subject(s)
Pyrimidine Nucleosides/isolation & purification , Streptomyces/chemistry , Crystallography, X-Ray , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , Molecular Structure , Pyrimidine Nucleosides/chemistry , Spectrum Analysis/methodsABSTRACT
A new medermycin analog (1) was isolated from the marine-derived actinomycetes Streptomyces sp. ZS-A45. The structure elucidation of compound 1 was determined by the HRESIMS and extensive NMR analysis. And compound 1 exhibited significant cytotoxicity against PC3 cell lines with IC50 values of 0.81 ± 0.42 µm.
Subject(s)
Actinobacteria/metabolism , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Line, Tumor , Circular Dichroism , Humans , Magnetic Resonance Spectroscopy , Marine Biology , Naphthoquinones/isolation & purificationABSTRACT
Six new (1-6) and nine known (7-15) staurosporine derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. NB-A13. The structures of the new staurosporine derivatives were established by extensive spectroscopic data interpretation. The absolute configurations of 1 and 2 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. All of these compounds were screened for their cytotoxic activities against PC-3 and SW-620 cell lines. Compound 7 exhibited stronger inhibitory activity against SW-620 cell lines than the positive control staurosporine (25.10â¯nM), with IC50 values of 9.99â¯nM. Moreover, compounds 1-5, 8-13 and 15 also showed significant cytotoxicities with IC50 values ranging from 0.02 to 16.60⯵M, while 6 exhibited no cytotoxic potency. Additionally, compounds 1-7 were also tested for enzyme inhibition activities of Protein kinase C theta (PKC-θ), and showed activity with IC50 values ranging from 0.06 to 9.43⯵M except for compound 6, which has no inhibition activity.
Subject(s)
Antineoplastic Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Staurosporine/analogs & derivatives , Staurosporine/pharmacology , Streptomyces/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Protein Kinase C-theta/antagonists & inhibitors , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/isolation & purification , Staurosporine/isolation & purification , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Four new medermycin-type naphthoquinones, strepoxepinmycins A-D (1-4), and one known compound, medermycin (5), were identified from Streptomyces sp. XMA39. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, strepoxepinmycin A (1) represents a rare 5,10-oxepindione ring system typically formed by a Baeyer-Villiger oxidation, and strepoxepinmycin B (2) is an isolation artifact derived from 1. Bioactivity evaluations of these compounds showed that compounds 3 and 4 exhibited cytotoxicity against HCT-116 and PC-3 cancer cell lines and 4 exhibited moderate inhibition of ROCK 2 protein kinase. In addition, all of the new compounds showed antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus and antifungal activity against Candida albicans.
Subject(s)
Naphthoquinones/isolation & purification , Streptomyces/metabolism , Water Microbiology , Anti-Infective Agents/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Naphthoquinones/chemistry , Naphthoquinones/pharmacologyABSTRACT
Nine new indolocarbazoles (1-9) were isolated from the marine-derived Streptomyces sp. DT-A61. Among them compounds 1-8 featured a hydroxy group at the C-3 or C-9 position. All purified compounds were identified by 1D and 2D NMR and HRESIMS data. The absolute configurations of 4-6, 8, and 9 were determined by electronic circular dichroism spectroscopic data. Compound 7 exhibited significant activity against human prostate PC-3 cancer cells with an IC50 value of 0.16 µM. Compounds 1, 5, 6, and 9 showed moderate inhibition against the same cell line with IC50 values of 8.0, 3.6, 3.1, and 5.6 µM. Compound 2 displayed a notable inhibitory effect against Rho-associated protein kinase (ROCK2) with an IC50 value of 5.7 nM, which was similar to the positive control staurosporine (IC50 7.8 nM).
Subject(s)
Aquatic Organisms/chemistry , Biological Factors/chemistry , Carbazoles/chemistry , Streptomyces/chemistry , Biological Factors/pharmacology , Carbazoles/pharmacology , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy/methods , PC-3 CellsABSTRACT
Eight new cyclizidine-type alkaloids (1-8) and one known alkaloid (9) were identified from the chemical investigations of a marine-derived actinomycete, Streptomyces sp. HNA39. Among these alkaloids, compounds 3, 7, and 8 contain a chlorine atom, and the known alkaloid, (+)-ent-cyclizidine (9), is now first reported as a natural product. Their structures were elucidated by extensive NMR-spectroscopic analysis and HRESIMS data. The absolute configurations of all of the compounds were established by ECD calculations. Cytotoxicity evaluations of all of the compounds showed that compound 2 exhibited significant activity against the PC3 and HCT116 human-cancer-cell lines with IC50 values of 0.52 ± 0.03 and 8.3 ± 0.1 µM, respectively. Interestingly, compounds 2, 5, 7, and 8 exhibited moderate inhibition against the ROCK2 protein kinase with IC50 values from 7.0 ± 0.8 to 42 ± 3 µM.
Subject(s)
Alkaloids/chemistry , Indolizidines/chemistry , Streptomyces/chemistry , Alkaloids/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , Cell Line, Tumor , Chlorine/chemistry , Chlorine/pharmacology , Cytotoxins/chemistry , Cytotoxins/pharmacology , HCT116 Cells , Humans , Indolizidines/pharmacology , Magnetic Resonance Spectroscopy/methods , PC-3 Cells , rho-Associated Kinases/antagonists & inhibitorsABSTRACT
On the basis of the one strain-many compounds strategy, five compounds including two new holomycin derivatives 2 - 3, two new cyclopropaneacetic acid derivatives 4 - 5, together with one known compound holomycin (1) were isolated from a marine-derived bacterium Streptomyces sp. DT-A37. Their structures were elucidated using NMR and HR-ESI-MS analyses. All these compounds were evaluated for their antimicrobial activity, cytotoxic activity, and inhibitory activity against BRD4 protein. Compound 1 exhibited potent cytotoxicity against H1975 cells with IC50 value of 1 µm, and its minimal inhibitory concentration values against Escherichia coli and Staphylococcus aureus were both 64 µm.
Subject(s)
Cyclopropanes/chemistry , Cyclopropanes/pharmacology , Lactams/chemistry , Lactams/pharmacology , Streptomyces/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Candida/drug effects , Candidiasis/drug therapy , Cell Cycle Proteins , Cell Line , Humans , Magnetic Resonance Spectroscopy , Nuclear Proteins/antagonists & inhibitors , Spectrometry, Mass, Electrospray Ionization , Transcription Factors/antagonists & inhibitorsABSTRACT
Four new analogues of brefeldin A named 7, 7-dimethoxybrefeldin C (3), 6ß-hydroxybrefeldin C (4), 4-epi-15-epi-brefeldin A (5), 4-epi-8α-hydroxy-15-epi-brefeldin C (6), together with four known analogues (1, 7-9) were isolated from a fermentation of the sediment-derived fungus Penicillium sp. DT-F29. The structures of these compounds were elucidated on the basis of extensive spectroscopic and chemical methods. In the bioactivity assays, only compounds 1 and 8 showed significant inhibitory activities against human lung adenocarcinoma cell. In addition, compound 1 was first reported for the potent ability to reactivate latent HIV with EC50 value of 0.03 µM.
Subject(s)
Anti-HIV Agents/pharmacology , Antineoplastic Agents/pharmacology , Brefeldin A/analogs & derivatives , Penicillium/chemistry , Anti-HIV Agents/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Evaluation, Preclinical , Geologic Sediments/microbiology , Humans , Molecular StructureABSTRACT
2-(Pro-1-ynyl)-5-(5,6-dihydroxypenta-1,3-diynyl) thiophene (PYDDT) is a naturally occurring thiophene isolated from the roots of Echinops grijsii, a Chinese herbal medicine used to treat colon cancer, breast cancer, and lung cancer. There are many reports on the clinical use of Echinops grijsii alone or in combination with other herbs to treat malignant tumors. We previously reported that the expression and activity of phase II enzymes including GSTs and NQO1 could be induced through the activation of Keap1-Nrf2 pathway by the treatment of PYDDT. In this study, we reported the anticancer effect and mechanism of PYDDT against human colon cancer SW620 cells. Our results demonstrate that treatment of SW620 cells with PYDDT leads to induction of mitochondrial-mediated apoptosis, which is characterized by the cleavage of PARP, activation of caspase 9 and caspase 3, release of cytochrome c from mitochondria, loss of mitochondrial membrane potential, down-regulation of Bcl-2, and mitochondrial translocation of Bax. The PYDDT treatment caused the production of reactive oxygen species (ROS), and the activation of JNK but not p38 mitogen-activated protein kinases and ERK1/2. Specific JNK inhibitor SP600125 prevented the PYDDT-induced down-regulation of Bcl-2, mitochondrial translocation of Bax, activation of caspase 3, and apoptosis of SW620 cells. Moreover, PYDDT-induced apoptosis as well as activation of JNK was abrogated by the pretreatment with antioxidant N-acetylcysteine. Taken together, these findings suggest that PYDDT induces apoptosis in SW620 cells through a ROS/JNK-mediated mitochondrial pathway.
Subject(s)
Apoptosis/drug effects , Colonic Neoplasms/metabolism , MAP Kinase Signaling System/drug effects , Reactive Oxygen Species/metabolism , Thiophenes/pharmacology , Apoptosis/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Colonic Neoplasms/drug therapy , Echinops Plant , Enzyme Activation/drug effects , Enzyme Activation/physiology , Humans , MAP Kinase Signaling System/physiology , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/physiology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Roots , Thiophenes/isolation & purification , Thiophenes/therapeutic useABSTRACT
The 95% ethanol extract of the whole plant of Physalis angulata Linn. afforded one new skeletal physalin named aminophysalin A (1) and one new naturally occurring 5ß-hydroxy-6a-chloro-5,6-dihydrophysalin B (2), together with five known physalins (3-7). Their structures were elucidated through MS, IR, NMR spectroscopy analyses and X-ray crystallography. Aminophysalin A (1) had an absolutely unusual structural feature in the chemistry of physalins with a nitrogen atom. Compounds 1-7 were evaluated for quinone reductase activities in hepa 1c1c7 cells. Physalin H (6) showed strong quinone reductase induction activity with IR (Induction ratio, QR induction activity) value of 3.74±0.02, using 4-bromoflavone as a positive control substance (2.17±0.01, 10 µg/mL), while compounds 1, 2, 3, 5 showed weak quinone reductase induction activity.
Subject(s)
Physalis/chemistry , Steroids/isolation & purification , Steroids/pharmacology , Cell Line , Enzyme Induction/drug effects , Ethanol/chemistry , Humans , NAD(P)H Dehydrogenase (Quinone)/biosynthesis , Steroids/chemistryABSTRACT
CONTEXT: Radix Curcumae is a traditional Chinese medicine that possesses antitumor properties, from which a new compound, diterpenoid C, was previously isolated and characterized. OBJECTIVE: In this study, using human colon adenocarcinoma SW620 cells, we further investigated the antitumor effects of diterpenoid C and the underlying mechanisms. MATERIALS AND METHODS: Cell proliferation was assessed with the MTT assay. Cell apoptosis and cell-cycle progression were analyzed with flow cytometry. The expression of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and their phosphorylated forms, as well as caspase-3 protein levels were examined with Western blots. RESULTS: Diterpenoid C could inhibit the proliferation of SW620 cells in a dose- and time-dependent manner. The median inhibitory concentration (IC50) at 24, 48, and 72 h were 28.31, 15.58, and 6.14 µg/ml, respectively. The inhibition of proliferation was found to be statistically significant as compared with the well-established drugs 5-fluorouracil (5-Fu) and oxaliplatin (L-OHP) (p < 0.01). Diterpenoid C also induced apoptosis and arrested cell cycle. It showed the highest apoptosis rate (98.20 ± 0.91%) at 70 µg/ml, at 72 h. Meanwhile, diterpenoid C suppressed the phosphorylation of ERK, JNK, and p38 MAPK proteins, and markedly induced the cleavage of caspase 3. DISCUSSION AND CONCLUSION: Diterpenoid C inhibits proliferation and induces apoptosis of cancer cells by suppressing the MAPK signaling pathway and inducing apoptotic factor caspase-3. Our results suggest that this novel compound might become a potent chemotherapeutic agent for the treatment of colon cancer and further studies are warranted.
Subject(s)
Adenocarcinoma/drug therapy , Colonic Neoplasms/drug therapy , Curcuma/chemistry , Diterpenes/pharmacology , Adenocarcinoma/pathology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Colonic Neoplasms/pathology , Diterpenes/administration & dosage , Diterpenes/isolation & purification , Fluorouracil/pharmacology , Humans , Inhibitory Concentration 50 , MAP Kinase Signaling System/drug effects , Organoplatinum Compounds/pharmacology , Oxaliplatin , Time FactorsABSTRACT
The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4µg/ml. So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure-activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camellia sinensis/chemistry , Saponins/pharmacology , Seeds/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Humans , Male , Mice , Mice, Inbred ICR , Molecular Structure , Saponins/chemistryABSTRACT
Phytochemical study on the ethanol extract of the radixes of Curcuma wenyujin Y. H. Chen et C. Ling led to the isolation of three new compounds curcuminol F (1) curcuminol G (2) and wenyujinoside (3) and a known compound aurantiamide (4). Their structures were elucidated on the basis of extensive spectroscopic analysis.
Subject(s)
Benzoates/isolation & purification , Curcuma/chemistry , Glucosides/isolation & purification , Plant Extracts/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Benzoates/chemistry , Glucosides/chemistry , Molecular Structure , Plant Extracts/isolation & purification , Plant RootsABSTRACT
Two novel thiophenes, grijisyne A (1), and grijisone A (2), were isolated from the crude ethanolic extract of the roots of Echinops grijissi Hance. Their structures were determined by spectral methods, especially 2D NMR spectra. All the isolated compounds were tested for their anti-tumor activities against three human tumor cell lines, HL-60, K562, and MCF-7.
Subject(s)
Echinops Plant/chemistry , Thiophenes/chemistry , Molecular Structure , Plant Roots/chemistryABSTRACT
Three new cycloartane glycosides were isolated from the whole herbs of Camptosorus sibiricus Rupr. By means of chemical and spectroscopic methods (IR, 1D, and 2D NMR, HR-MS, ESI-MS), the structures were established as (24R)-3beta,7beta,24,25, 30-pentahydroxycycloartane-3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-beta-D-glucopyranosyl]-24-O-beta-D-glucopyranoside (1), (24R)-3beta,7beta,24,25,30-pentahydroxycycloartane-3-O-beta-D-glucopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucopyranosyl]-24-O-beta-D-glucopyranoside (2), (24R)-3beta,7beta,24,25,30-pentahydroxycycloartane-30-O-coumaroyl-3-O-beta-D-glucopyranosyl-24-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (3). At the same time, the new compounds were tested for their cytotoxicities in vitro against human tumor cell lines (A375-S2, Hela) using MTT method.
Subject(s)
Ferns/chemistry , Glycosides/chemistry , Triterpenes/chemistry , Molecular StructureABSTRACT
From the fruits of Celastrus orbiculatus Thunb. a new beta-dihydroagarofuran sesquiterpene ester named 1beta,2beta,13-triacetoxy-9alpha-cinnamoyloxy-beta-dihydroagarofuran (1) has been isolated along with two known compounds, 6alpha-acetoxy-1beta,9beta-dibenzoyloxy-8beta-hydroxy-beta-dihydroagarofuran (2), and 1beta, 6alpha-diacetoxy-9beta-benzoyloxy-8beta-hydroxy-beta-dihydroagarofuran (3). Their structures were elucidated on the basis of spectroscopic data.