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Natural products are well established as an important resource and play an important role in drug discovery. Here, two pyrrolinone-fused benzoazepine alkaloids, (+)-asperazepanones A (1) and B (2) with a 6/7/5 ring system, together with the artifact (−)-asperazepanone A (1), were isolated from the coral-derived Aspergillus candidus fungus. Their st...
Citations
... The X-ray data ( Figure 5) revealed that 4 possessed a centrosymmetric space group P 121/c 1, showing recemic nature. [25] An HPLC analysis was carried out using a chiral column to obtain compounds 4a and 4b . The absolute configurations of 4a and 4b were assigned as 1'R ,3'S ,4'S ,6'S , and 1'S ,3'R ,4'R ,6'R , by comparision of experimental and calculated ECD spectra, respectively. ...
Ten novel isocoumarins, including four pairs of enantiomers, were isolated from Artemisia dubia var. subdigitata (Asteraceae). Com-pounds 1, 2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-methylcyclohexyl) propan-1-one moiety fused with isocoumarin core skeleton. Compounds 4a/4b were characterized as an unexpected 2,5-dimethylcyclohexan-1-one scaffold, and compounds 5a/5b and 6a/6b were rare 1,2-seco-isocoumarin. Their structures and absolute configurations were elucidated through spectroscopic data, X-ray crystallography, ECD and NMR calculations with DP4+ analyses. Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin. Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and PI3K-Akt signaling pathway. The molecular docking revealed that compound 1 had high binding affinity with CDK2 (total score: 6.8717). Furthermore, compounds 1 and 2 exhibited inhibitory activity on three human hepa-toma cell lines, with inhibitory ratios of 85.1% and 84.5% (HepG2), 88.2% and 87.3% (Huh7), and 69.2% and 69.1% (SK-Hep-1) at 200 μM, respectively.
... The spontaneous transformation of natural products is an unusual phenomenon, and some examples of these reactions include keto-enol tautomerism, keto-amide tautomerism, and the ring opening and closing of α, β-unsaturated-γ-hydroxyl-γ-lactone [8][9][10][11][12][13][14]. In addition, the reactions of neighboring groups within molecules could cause spontaneous transformation in compounds. ...
... After the partition, the EtoAc-soluble part was investigated under the guidance of a UV spectrum obtained from HPLC-DAD for the directional separation of lindenanetype sesquiterpenes. As a result, ten known compounds ( Figure 2) were isolated and elucidated as shizukaol C (4) [17], chlorahololide D (5) [18], chololactone F (6) [19], shizukaol The spontaneous transformation of natural products is an unusual phenomenon, and some examples of these reactions include keto-enol tautomerism, keto-amide tautomerism, and the ring opening and closing of α, β-unsaturated-γ-hydroxyl-γ-lactone [8][9][10][11][12][13][14]. In addition, the reactions of neighboring groups within molecules could cause spontaneous transformation in compounds. ...
... Therefore, the MS analysis of HPLC-HR-MS could be very suitable for monitoring the occurrence of these reactions. For the former method, purified shizukaol C (4), chololactone F (6), shizukaol D (9), fortunilide C (10), 13'-dehydroxylation-sarcandrolide J (11), and sarglabolide J (12) were placed in solution to detect the transformation. After 30 days of simulations, we used HPLC-HR-MS to detect and analyze the solution. ...
In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of Chloranthus fortunei. As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (1–3), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15’ and C-13’ of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4β-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity.
... Tautomeric and stereoisomerized compounds are common in the field of natural products research, especially for ketone− enol, 1−4 enamine−imino, 5 hemiketal−aldol, 6,7 and (retro-)oxa-Micheal addition 8 tautomerism. Convincing hypotheses were proposed to clarify the converting mechanism, and NMR calculation, acid or alkali treatment, chiral-phase high-performance liquid chromatography (HPLC) analysis, and methylation reactions were reported to verify some of those hypotheses. ...
... In the meanwhile, (±)-3 were also isolated by using HPLC with the same chiral-ND column, respectively, at t R = 7.5 and 10.0 min (the gradient was n-hexane/2-propanol v/v, 80:20, flow rate: 1 mL/min), and the structures of (±)-3 were determined by comparing their NMR data to cytosporone D. 9 Similarly, (±)-3 showed the enantiomerization equilibrium appearance with HPLC-DAD analysis. 5 C-1 and C-6′ were two chiral centers of 1 and 2, and C-1 was the unique chiral center of (±)-3. Sharing the similar converting behavior indicated that C-1 was the key to the converting mechanism, and configuration of C-6′ of 1 is the same as 2, because it is unlikely for a chiral carbon's configuration converting on an aliphatic chain in this very situation, which could be further supported by their chemical shifts (δ H -1′ 1.84 in 1 while at δ H -1′ 1.83 in 2). ...
... To verify hypotheses that is similar to the above plausible mechanism, methylation methods were performed in previously reported articles. 4,5 Likewise, methylation reactions of the hydroxyl groups of 1 and 2 with different reagents were applied: (i) sodium hydride and iodomethane, (ii) and (iii) thionyl chloride (SOCl 2 ) in methanol (MeOH) in different addition sequences, and (iv) (trimethylsilyl)diazomethane (TMS-CHN 2 ). The conditions and the results are listed in Table 2. ...
Two new octaketides, cytosporones W (1) and X (2), along with eight known cytosporone derivatives [(±)-3-9], were isolated from mangrove endophytic fungus Diaporthe sp. ZJHJYZ-1. Compounds 1 and 2 were a pair of epimers, whose configuration of C-1 could mutually convert, causing racemization of the lactone ring. The planar structures of compounds were elucidated through detailed 1D, 2D NMR, and HR-ESI-MS analysis. ECD spectra comparison and modified Mosher ester method were applied to determine the absolute configuration of 1 and 2. In bioassays, (±)-3 exhibited promising inhibitory activities against Bacillus subtilis, Pseudomonas aeruginosa, and Penicillium italicum with MIC, respectively, for 12.5, 12.5, and 3.13 μM.
... A modern and interesting direction of research is the design and study of ways to incorporate non-steroidal anti-inflammatory drugs (NSAIDs), agents frequently prescribed in medical practice for various diseases accompanied by pain, fever or inflammation (8,9). The phenylacetic acid derivative diclofenac is a NSAIDs with potent anti-inflammatory activity but also with a high risk of gastric irritation (9,22). In order to reduce the number of admin- istrations of such a drug, with a short halflife, there is a need to obtain sustainedrelease systems, formulations, whose oral use could diminish the adverse gastrointestinal effects (6, 7). ...
... In the current study, we chose diclofenac (DCF) from the NSAID group, known to have strong anti-inflammatory effects, but also many side effects, especially in the gastrointestinal tract [26][27][28]. DCF is a phenylacetic acid derivative with an acidity constant of 4 (therefore considered a weak acid) and a partition coefficient of 13.4 (which indicates a partial solubility in both aqueous and hydrophobic media). The structural features of the molecule, namely the presence of the phenylacetic acid group and a phenyl ring containing two chlorine atoms, facilitate the maximum torsion of the phenyl ring [29], which ensures a good fit in the coupling to the appropriate substrate binding pocket at cyclooxygenase enzyme (COX) [30]. ...
The purpose of our study was the obtaining, characterization and biocompatibility estimation of novel carrier systems for diclofenac. Diclofenac is a potent nonsteroidal anti-inflammatory drug with frequent gastrointestinal side effects, impairing the quality of the patient’s life. Original diclofenac-loaded micro-vesicles coated with chitosan were prepared and physico-chemical analyzed. We investigated their in vitro hemocompatibility and in vivo biocompatibility in rats. The animals were treated orally as follows: group 1 (Control): distilled water 0.3 mL/100 g body weight; Group 2 (CHIT): 0.3 mL/100 g body weight 0.5% chitosan solution; Group 3 (DCF): 15 mg/kg body weight diclofenac; Group 4 (DCF-ves): lipid vesicles loaded with diclofenac 15 mg/kg body weight. Blood samples were collected for assessing: red blood cells, hemoglobin, hematocrit and leukocyte formula. A series of specific parameters of the liver and kidney function, some markers of immune defense, as well as the activity of some enzymes involved in oxidative processes, were also investigated. At the end of the experiment, the animals were sacrificed and fragments of liver, kidney and stomach were collected for histopathological examination. No blood hemolysis was evidenced by the in vitro test with the administration of diclofenac vesicles. The animals treated with diclofenac lipid vesicles stabilized with chitosan did not display any notable differences in their hematological and biochemical profile compared to control animals. These data correlated with the histological results, which showed the absence of architectural changes in the examined tissues. Biological in vitro and in vivo evaluation revealed that the microvesicles containing diclofenac are biocompatible, with potential to be used as delivery systems to modify the drug release, thus making them an attractive candidate for biomedical applications.
Comprehensive Summary
Ten novel isocoumarins, including four pairs of enantiomers, were isolated from Artemisia dubia var. subdigitata (Asteraceae) . Compounds 1 , 2 and 3a / 3b possessed a unique 6/6/6‐tricyclic system comprising an unusual 1‐(2‐methylcyclohexyl) propan‐1‐one moiety fused with isocoumarin core skeleton. Compounds 4a / 4b were characterized as an unexpected 2,5‐dimethylcyclohexan‐1‐one scaffold, and compounds 5a / 5b and 6a / 6b were rare 1,2‐ seco ‐isocoumarin. Their structures and absolute configurations were elucidated through spectroscopic data, X‐ray crystallography, ECD and NMR calculations with DP4+ analyses. Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin. Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and PI3K‐Akt signaling pathway. The molecular docking revealed that compound 1 had high binding affinity with CDK2 (total score: 6.8717). Furthermore, compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines, with inhibitory ratios of 85.1% and 84.5% (HepG2), 88.2% and 87.3% (Huh7), and 69.2% and 69.1% (SK‐Hep‐1) at 200 μmol·L –1 , respectively.
A comprehensive review of 1411 new MNPs and their structural diversity analysis and including the cyanobacterial metabolite lezoside.
