Change in thermal stability and molecular structure characteristics of whey protein beta-lactoglobulin upon the interaction with levamisole hydrochloride.

The interaction between beta-lactoglobulin (BLG) and anthelmintic compounds including levamisole (LEV) is a matter of great concern as it not only poses potential health and environmental risks but also has significant implications for food processing and production. The mechanisms of LEV-BLG interaction were investigated through spectral and molecular modeling approaches. Fluorescence and UV-Visible investigations indicated the formation of a spontaneous and stable LEV-BLG complex. Structural changes of BLG were revealed by circular dichroism and Fourier transform infrared studies. The thermal stability of BLG increased in the presence of LEV. Molecular docking studies indicated the best mode of LEV-BLG interaction and molecular dynamics simulation confirmed the stability of the LEV-BLG complex. In conclusion, our study sheds light on the potential of BLG to interact with deleterious substances such as anthelmintic agents, thus highlighting the necessity of further research in this field to assure food safety and prevent any health hazards.

Molecular structure, spectral analysis and chemical activity of sabizabulin: A computational study.

In this study, a detailed computational spectroscopic investigation of sabizabulin, a small molecule known as a tubulin inhibitor with potential antineoplastic, antiviral, and anti-inflammatory activities, has been presented. Our work utilizes Density Functional Theory (DFT) calculations to explore molecular optimization, thermodynamic characteristics, and the analysis of normal modes with vibrational assignments. We calculate essential properties such as standard zero-point vibrational energy, entropy, dipole moment, etc., based on data extracted from the optimized molecular structure. Additionally, we examine Mulliken charges and the Molecular Electrostatic Potential (MEP) plot to comprehend the electronic distribution and chemical activity of sabizabulin. Our findings provide valuable insights into the spectroscopic properties of sabizabulin, highlighting its potential therapeutic applications. Our work aims to explore future research directions that could expand the understanding of sabizabulin's actions and enhance its applicability in medical treatments.

Seven new secondary metabolites isolated from roots of Lespedeza bicolor.

Chemical investigation of a methanol extract obtained from the roots of Lespedeza bicolor identified one new pterocarpene (1), three new pterocarpans (2-4), and three new arylbenzofurans (5-7), and two known compounds (8 and 9). Their structures were determined by interpretations obtained from combined UV, NMR, and HRTOFMS spectroscopic data. Furthermore, the absolute configurations of compounds 2 and 3 were established by the combination of electronic circular dichroism (ECD) calculations and NMR calculations with DP4+ probability analysis. All isolated compounds (1-9) were evaluated for cytotoxicity against the human lung carcinoma cell line A549 and the human hepatoma cell line Huh-7. Compound 4 showed antiproliferative activity against A549 cell line with IC50 value of 24.9 µM. Furthermore, compound 9 exhibited cytotoxicity against Huh-7 cell line with IC50 value of 68.7 µM.

Molecular Structure of Gaseous Oxopivalate Co(II): Electronic States of Various Multiplicities.

Synchronous electron diffraction/mass spectrometry was used to study the composition and structure of molecular forms existing in a saturated vapor of cobalt(II) oxopivalate at T = 410 K. It was found that monomeric complexes Co4O(piv)6 dominate in the vapor. The complex geometry possesses the C3 symmetry with bond lengths Co-Oc = 1.975(5) Å and Co-O = 1.963(5) Å, as well as bond angles Oc-Co-O = 111.8(3)°, Co-Oc-Co = 110.4(6)°, O-Co-O = 107.1(3)° in the central OcCo4 fragment and four OcCoO3 fragments. The presence of an open 3d shell for each Co atom leads to the possibility of the existence of electronic states of the Co4O(piv)6 complex with Multiplicities 1, 3, 5, 7, 9, 11, and 13. For them, the CASSCF and XMCQDPT2 calculations predict similar energies, identical shapes of active orbitals, and geometric parameters, the difference between which is comparable with the error of determination by the electron diffraction experiment. QTAIM and NBO analysis show that the Co-Oc and Co-O bonds can be attributed to ionic (or coordination) bonds with a significant contribution of the covalent component. The high volatility and simple vapor composition make it possible to recommend cobalt (II) oxopivalate as precursors in the preparation of oxide films or coatings in the CVD technologies. The features of the electronic and geometric structure of the Co4O(piv)6 complex allows for the conclude that only a very small change in energy is required for the transition from antiferromagnetically to ferromagnetically coupled Co atoms.

Structurally Diverse Metabolites from the Marine-Derived Streptomyces sp. DS-27 Based on Two Different Culture Conditions.

Nine new compounds, including streptothiomycin A-E (1-5), two cyclopentenones (6, 7), one α-pyrone (8), wailupemycin Q (20), along with sixteen known compounds were identified from a rhizosphere strain Streptomyces sp. DS-27 derived from the marine cordgrass Spartina alterniflora under two different culture conditions. All of the structures were elucidated by extensive analysis of 1D/2D NMR and HR-ESI-MS data. The absolute configurations were determined by NOESY analysis, ECD, specific rotation and GIAO NMR calculations, and DP4+ probability analysis. Bioactivity investigation showed that compounds 5 and 7 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Design, Synthesis, Molecular Modelling and in Vitro Evaluation of Indolyl Ketohydrazide-Hydrazone Analogs as Potential Pancreatic Lipase Inhibitors.

Inhibition of Pancreatic lipase (PL) is considered to be a promising target for the management of obesity, owing to its crucial role in the digestion of dietary triglycerides. A series of 31 indolyl ketohydrazide-hydrazone analogs (5 aa-cm) were designed, synthesized and evaluated for their PL inhibitory potential. The analogs were designed using molecular modelling studies. The designed analogs were then synthesized by condensation of indolyl oxoacetohydrazide with various substituted benzaldehydes. All the synthesized analogs showed PL inhibitory activity in the range of 4.13-48.35 µM, as compared with orlistat (0.86±0.09 µM). The most potent analog 5 bi (IC50 =4.13±0.95 µM) was found to show a competitive type of inhibition with Ki value of 0.725 µM. Additionally, the molecular docking study proved the binding of analog 5 bi at the active site of PL (PDB ID: 1LPB) with MolDock score of -141.279 kcal/mol. It also exhibited various interactions with the key amino acids namely Phe77, Phe215, Tyr114, Ser152, Arg256, His263, etc. Furthermore, the protein-ligand complex of analog 5 bi was found to be stable in molecular dynamics simulation for 100 ns with RMSD of less than 3.2 and 4 Šfor the protein and ligand, respectively. The current work hereby provides a basis for the potential role of indolyl ketohydrazide-hydrazone analogs in PL inhibition and further optimization could result in the generation of new leads as anti-obesity agents.

Furfural Derivatives and Phenolic Constituents in Stemona tuberosa Lour.

Chemical investigation on the water-soluble constituents of Stemona tuberosa Lour. resulted in the isolation of a previously undescribed furfural derivative namely (S)-5-((R)-hydroxy(5-(hydroxymethyl)furan-2-yl)methyl)-5-methylfuran-2(5H)-one and twenty-five known compounds from the water decoction of the dried root tubers. Their structures were determined by analysis of the extensive spectroscopic data, including 1D/2D NMR, HR-ESI-MS, and ORD, as well as the ECD simulation and comparison. Most of them were phenolic and among them, four compounds were isolated from Stemona plants for the first time. This study uncovers diverse constituents from water decoction of S. tuberosa dedicated for its quality control and allows for the exploitation of chemical markers with potential significance for discrimination of Stemona plants.

Undescribed Phenolic Glycosides from Syzygium attopeuense and Their Inhibition of Nitric Oxide Production.

Four undescribed phenolic glycosides including three stilbene derivatives (1 and 3) and sodium salt of 3 (2), and a chalcone glycoside (4), together with thirteen known compounds (5-17) were isolated from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry. Their chemical structures were elucidated to be (Z)-gaylussacin (1), 6''-O-galloylgaylussacin sodium salt (2), 6''-O-galloylgaylussacin (3), 4'-O-[ß-D-glucopyranosyl-(1→6)-glucopyranosyl]oxy-2'-hydroxy-6'-methoxydihydrochalcone (4), gaylussacin (5), pinosilvin 3-O-ß-D-glucopyranoside (6), myricetin-3-O-(2''-O-galloyl)-α-L-rhamnopyranoside (7), myricetin-3-O-(3''-O-galloyl)-α-L-rhamnopyranoside (8), myricetin-3-O-α-L-rhamnopyranoside (9), quercitrin (10), myricetin-3-O-ß-D-glucopyranoside (11), myricetin-3-O-ß-D-galactopyranoside (12), quercetin 3-O-α-L-arabinopyranoside (13), myricetin-3-O-2''-O-galloyl)-α-L-arabinopyranoside (14), (+)-gallocatechin (15), (-)-epigallocatechin (16), and 3,3',4'-trimethoxyellagic acid 4-O-ß-D-glucopyranoside (17) by the analysis of HR-ESI-MS, 1D and 2D NMR spectra in comparison with the previously reported data. Compounds 1-3, 5, and 6 significant inhibition of NO production in LPS-activated RAW264.7 cells, with IC50 values ranging from 18.37±1.38 to 35.12±2.53 µM, compared to a positive control (dexamethasone) with an IC50 value of 15.37±1.42 µM.

Three New Labdane-Type Diterpenoids from the Fruits of Amomum villosum and Their Anti-Inflammatory Activities.

Three new labdane-type diterpenoids, calcaratarin E, villosumtriol, and 12-epi-villosumtriol (1-3) were isolated from the fruits of Amomum villosum, along with seven known diterpenoids (4-10). Through comprehensive analysis of chemical evidence and spectral data including UV, 1D and 2D NMR, HR-ESI-MS, IR, and X-ray crystallography, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 2-10 on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Notably, compound 6 exhibited the most significant inhibitory effect with an IC50 value of 1.74±0.69 µM.

New Guaiane-Type Sesquiterpene and Norsesquiterpene from Alisma plantago-aquatica and Their Xanthine Oxidase Inhibitory Activity.

A new sesquiterpene (1) and a new norsesquiterpene (2) belonging guaiane-type skeleton together with six known compounds (3-8) were isolated from the rhizomes of Alisma plantago-aquatica. Their structures were determined by HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Absolute configurations of new compounds were established by experimental and TD-DFT computational ECD spectra. Compounds 1-8 exhibited xanthine oxidase inhibitory activity with their IC50 values in range of 9.4-66.7 µM. The sesquiterpenoids 1-5 displayed the inhibitory activity and hence they could be potential xanthine oxidase inhibitors from A. plantago-aquatica.

Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Structurally Diverse Sesquiterpenoids from the Genus of Ainsliaea.

The genus of Ainsliaea embraces approximately 70 recognized species, many of which have been used to treat various diseases in folklore medicines. As the main metabolites of Ainsliaea plants, Ainsliaea sesquiterpenoids have drawn considerable attention in related scientific communities due to their intriguing structures and a variety of bioactivities. In this review, we intend to provide a full-aspect coverage of sesquiterpenoids reported from the genus of Ainsliaea, including 145 monomeric sesquiterpenoids and 30 oligomeric ones. Multiple aspects will be summarized, including their classification, distributions, structures, bioactivities, and biomimetic syntheses. In addition, their possible biosynthetic pathway will be discussed in detail.

In-vitro anticancer evaluation of newly designed and characterized tri/tetra-substituted imidazole congeners- maternal embryonic leucine zipper kinase inhibitors: Molecular docking and MD simulation approaches.

Our cascading attempt to develop new potent molecules now involves designing a series of imidazole derivatives and synthesizing two sets of 2,4,5- tri-substituted (4a-4d) and 1,2,4,5-tetra-substituted (6a-6d) imidazole by the principle of Debus-Radziszewski multicomponent synthesis reaction. The structures of the obtained compounds were confirmed by 1H/13C NMR, FT-IR, elemental analysis, purity and the retention time was analyzed by HPLC. Based upon the binding affinity in the molecular docking studies, we have synthesized different imidazole derivatives from which compound 6c have been found to show more anti-proliferative activity by inducing apoptosis at a higher rate than the other compounds corroborating the in-silico prediction. The structure and crystallinity of compound 4d have been confirmed by single XRD analysis. The synthesized molecules were screened for their in vitro anti-cancer properties in triple negative breast cancer cell line (MDA-MB-231), pancreatic cancer cell lines (MIA PaCa-2) and oral squamous cell carcinoma cell line (H357) and results indicated that all the compounds inhibited the cell proliferation in a concentration-dependent manner at different time points. The compounds 4b and 6d were found to be effective against the S. aureus bacterial strain whereas only compound 4d fairly inhibited the fungal strain of T. rubrum with a MIC 12.5 µg/mL. Molecular docking study reveals good interaction of the synthesized compounds with known target MELK involved in oncogenesis having high binding profiles. The lead compound 6c was further analyzed by the detailed molecular dynamics study to establish the stability of the ligand-enzyme complex.

Ormosianines A-P, Structurally Diverse Quinolizidine Alkaloids with AChE Inhibitory Effects from Ormosia yunnanensis.

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.

HIV-1 Integrase Inhibitor, Dihydroobionin B, and the Investigation of Its Extraordinary Specific Rotation.

Dihydroobionin B (1), a chiral congener of known obionin B, was isolated from Pseudocoleophoma sp. KT4119, a freshwater fungus collected from a submerged wood block in Kochi Prefecture, Japan, in 2020. The planar structure of 1 was characterized by mass and NMR spectral analysis and confirmed by density functional theory (DFT)-based chemical shift calculations. Its absolute structure was determined by electronic circular dichroism spectral analysis. Notably, 1 exhibited an extraordinarily large specific rotation [[α]20D +1080 (c 0.056, CHCl3)], which was verified by DFT-based specific rotation calculations. However, these calculations indicated that the sign of the specific rotation based on static analysis was insufficient to determine the absolute configuration in this case. Furthermore, Pseudocoleophoma KT4119 produced coleophomapyrones A (2) and B (3) and coleophomaldehyde A (4). While this is the first report of 2 isolated from a natural source, it has also been prepared previously using a synthetic approach. Compound 1 potently inhibited HIV type 1 integrase (IC50 = 0.44 µM) without significant cytotoxicity. Finally, docking experiments were conducted to propose a plausible mechanism for the behavior of 1.

Cyclotheonellazoles D-I, Potent Elastase Inhibitory Thiazole-Containing Cyclic Peptides from Theonella sp. (2131).

Six new thiazole-containing cyclic peptides, the cyclotheonellazoles D-I (1-6), were isolated from the Australian marine sponge Theonella sp. (2131) with their structures assigned by comprehensive 1D and 2D NMR spectroscopic and MS spectrometric analyses, Marfey's derivatization studies, and comparison with time-dependent density functional theory (TDDFT) calculated ECD data. The Type 2 azole-homologated peptides herein comprise up to five nonproteinogenic amino acids, including the protease transition state mimic α-keto-ß-amino acid residue 3-amino-4-methyl-2-oxohexanoic acid (Amoha), while 1-3 also contain a terminal hydantoin residue not previously found in cyclotheonellazoles. The keramamides A (7) and L (8) were reisolated affording expanded exploration of their biological activities. The peptides were examined for protease inhibitory activities against two mammalian serine proteases (elastase and chymotrypsin) and SARS-CoV-2 3-chymotrypsin-like protease (3CLpro), a validated antiviral therapeutic target for COVID-19. Peptides 1-6 and keramamide A (7) displayed potent nanomolar inhibition of elastase (IC50 16.0 to 61.8 nM), while 7 also contained modest inhibition of chymotrypsin and SARS-CoV-2 3CLpro (IC50 0.73 and 1.1 µM, respectively). The cyclotheonellazoles D-E (1-3) do not affect the viability of human breast, ovarian, and colon cancer cells (>100 µM), with the cytotoxicity previously reported for keramamide L (8) not replicated (inactive >20 µM).

Coscinoderines A-J: Trisubstituted Pyridinium-Containing Norterpenoids Isolated from Coscinoderma bakusi, a Tropical Marine Sponge.

Ten new norterpene alkaloids, coscinoderines A-J (1-10), were isolated from the marine sponge Coscinoderma bakusi. Each coscinoderine contains a 1,2,5-trisubstituted pyridinium moiety bearing a terpene unit at the C-2 position. Their structures were elucidated by analysis of NMR and HRMS data, and the absolute stereochemistry of 4 with a 2-methylbutyl group attached to the nitrogen was determined from a comparison of the calculated and measured ECD spectra. The isolation of coscinoderines expands the repertoire of pyridinium alkaloids isolated from marine sponges.

Bioactive Isoquinoline Alkaloids with Diverse Skeletons from Fissistigma polyanthum.

Six new isoquinoline alkaloids, including aporphine alkaloids (2, 3, 9, and 10), a benzylisoquinoline alkaloid (13), and a protoberberine alkaloid (17), were isolated from the roots of Fissistigma polyanthum, along with a new furanone (20) and 13 known isoquinoline alkaloids (1, 4-8, 11, 12, 14-16, 18, and 19). The structures of the new compounds were elucidated by the analysis of spectroscopic data. Compounds 1 and 2 are rare oxalyl-fused dehydroaporphine alkaloids. Compound 12 presented the most potent dual-target activities on AChE inhibition and Aß aggregation inhibition, while compounds 13 and 19 simultaneously exhibited discernible AChE and BChE inhibitions with antioxidant activities. The activity results indicate that F. polyanthum alkaloids have a potential of inhibition and prevention of Alzheimer's disease mainly through both ChEs and ß-amyloid pathways in addition to antioxidant activity.

Effect of Flattened Structures of Molecules and Materials on Machine Learning Model Training.

A key aspect of producing accurate and reliable machine learning models for the prediction of properties of quantum chemistry (QC) data is identifying possible data characteristics that may negatively influence model training. In previous work, we identified that molecules and materials with a low volume of the convex hull (VCH) of atomic positions may be harmful in model training and a source of prediction outliers. In this paper, we extend this analysis further and develop a biased sampling study to evaluate the influence of VCH on the training data of a model using different structures of molecules and materials. Our study confirms that VCH influences model training and shows the importance of using homogeneous geometric characteristics of structures when building new data sets or selecting training sets from larger QC data sets.

Synthesis and Computational Exploration of Morpholine Bearing Halogenated Sulfonamides as Potential Tyrosinase Inhibitors.

In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1 H-NMR & 13 C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025 µM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.