Density Functional Theory Analysis Research Articles

Synthesis, characterization, molecular docking, and antimicrobial activities of some new sulfur containing norfloxacin analogues

The in vitro antimicrobial activity was investigated for two new series of N-4 piperazinyl sulfur containing Ketene S,S-acetals and Ketene N,S-acetals, based norfloxacin analogues against two pathogenic fungi and four pathogenic Gram-positive and Gram-negative bacterial strains. The majority of synthetic compounds exhibit comparable efficacy to norfloxacin against the four tested bacteria. The MIC of the compounds varied from 1.56 to 50 µg/ml. Compounds 8, 9, and 10 exhibited good antifungal activities compared to Griseofulvin. Most of the tested compounds showed promising antibacterial activity. Compounds 4, 9 and 10 showed twice the activity against E. coli (MIC = 3.12 µg/ml), while 6 showed twice the activity against P. aeruginosa (MIC = 6.25 µg/ml), compared to norfloxacin. Similarly, 5 and 9 showed double the activity against k. pneumonia (MIC = 3.12 µg/ml) and 3 showed higher activity against the Gram positive S. aureus. Compounds 1–10 underwent a comprehensive molecular docking investigation with 1HNJ protein from E. coli and showed diverse binding. The binding affinities, expressed as docking scores (S, kcal/mol), exhibited a range from −8.67 (9), −8.47 (10), and −8.45 (8), to −6.85 (7), and −6.47 (3) Kcal/mol. The outcomes of this investigation provide compelling evidence for the inhibitory potential of these compounds against 1HNJ, suggesting a new 1HNJ-targeting agents. Results of Density Functional Theory analysis for 8, 9 and 10 and norfloxacin showed that the calculated HOMO-LUMO energy differences (ΔE), softness, and hardness for compounds 8, 9 and 10 were found to be comparable to that of norfloxacin, emphasizing the significance of charge transfer at the molecular level.

The Physical Mechanism of Linear and Nonlinear Optical Properties of Nanographene-Induced Chiral Inversion.

Based on density functional theory (DFT) and wave function analysis, the ultraviolet and visible spectrophotometry (UV-Vis) spectra and Raman spectra of 1-meso and 1-rac obtained by the chiral separation of chiral nanographenes are theoretically investigated. The electron excitation properties of 1-meso and 1-rac are studied by means of transition density matrix (TDM) and charge density difference (CDD) diagrams. The intermolecular interaction is discussed based on an independent gradient model based on Hirshfeld partition (IGMH). The interaction of 1-meso and 1-rac with the external environment is studied using the electrostatic potential (ESP), and the electron delocalization degree of 1-meso and 1-rac is studied based on the magnetically induced current under the external magnetic field. Through the chiral separation of 1-rac, two enantiomers, 1-(P, P) and 1-(M, M), were obtained. The electrical-magnetic interaction of the molecule is revealed by analyzing the electron circular dichroism (ECD) spectra of 1-meso, 1-(P, P) and 1-(M, M), the transition electric dipole moment (TEDM) and the transition magnetic dipole moment (TMDM). It is found that 1-(P, P) and 1-(M, M) have opposite chiral properties due to the inversion of the structure.

Building Feedback-Regulation System Through Atomic Design for Highly Active SO2 Sensing.

Reasonably constructing an atomic interface is pronouncedly essential for surface-related gas-sensing reaction. Herein, we present an ingenious feedback-regulation system by changing the interactional mode between single Pt atoms and adjacent S species for high-efficiency SO2 sensing. We found that the single Pt sites on the MoS2 surface can induce easier volatilization of adjacent S species to activate the whole inert S plane. Reversely, the activated S species can provide a feedback role in tailoring the antibonding-orbital electronic occupancy state of Pt atoms, thus creating a combined system involving S vacancy-assisted single Pt sites (Pt-Vs) to synergistically improve the adsorption ability of SO2 gas molecules. Furthermore, in situ Raman, ex situ X-ray photoelectron spectroscopy testing and density functional theory analysis demonstrate the intact feedback-regulation system can expand the electron transfer path from single Pt sites to whole Pt-MoS2 supports in SO2 gas atmosphere. Equipped with wireless-sensing modules, the final Pt1-MoS2-def sensors array can further realize real-time monitoring of SO2 levels and cloud-data storage for plant growth. Such a fundamental understanding of the intrinsic link between atomic interface and sensing mechanism is thus expected to broaden the rational design of highly effective gas sensors.

Ligand based-design of potential schistosomiasis inhibitors through QSAR, homology modeling, molecular dynamics, pharmacokinetics, and DFT studies

ObjectivesSchistosomiasis, a neglected tropical disease, is a leading cause of mortality in affected geographic areas. Currently, because no vaccine for schistosomiasis is available, control measures rely on widespread administration of the drug praziquantel (PZQ). The mass administration of PZQ has prompted concerns regarding the emergence of drug resistance. Therefore, new therapeutic targets and potential compounds are necessary to combat schistosomiasis. MethodsTwenty-four potent derivatives of PZQ were optimized via density functional theory (DFT) at the B3LYP/6-31G∗ level. Quantitative structureactivity relationship (QSAR) models were generated and statistically validated, and a lead candidate was selected to develop therapeutic options with improved efficacy against schistosomiasis. The biological and binding energies of the designed compounds were evaluated. In addition, molecular dynamics; drug-likeness; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and DFT studies were performed on the newly designed compounds. ResultsFive QSAR models were generated, among which model 1 had favorable validation parameters (R2train: 0.957, R2adj: 0.941, LOF: 0.101, Q2cv: 0.906, and R2test: 0.783) and was chosen to identify a lead candidate. Other statistical parameters for the chosen model included variance inflation factor values ranging from 1.242 to 1.678, and a Y-scrambling coefficient (cRp2) of 0.747. Five new compounds were designed with improved predicted activity (ranging from 5.081 to 7.022) surpassing those of both the lead compound and PZQ (predicted pEC50 of 5.545). Molecular dynamics simulation revealed high binding affinity of the proposed compounds toward the target receptor. ADMET and drug-likeness assessments indicated adherence to Lipinski's rule of five criteria, thereby suggesting pharmacological and oral safety. In addition, DFT analysis indicated resistance to electronic alteration during chemical reactions. ConclusionThe proposed compounds exhibited potential drug characteristics, thus indicating their suitability for further investigation to enhance schistosomiasis treatment options.

First‐Principles Calculations to Investigate the Ground State, Mechanical Stability, Electronic Structure, and Optical Properties of Tl2SnX3 (X = S, Se, Te)

AbstractIn this work, the Density Functional Theory (DFT) analysis of the Tl2SnX3 series (X = S, Se, Te) is performed, and the ground states are confirmed by the calculation of the elastic constant Cij. Based on the DFT calculation, the Tl2SnX3 structures are direct‐gap semiconductors with bandgaps of 1.434, 1.181, and 0.907 eV, respectively. Chalcogen substitution significantly impacts their electronic structures, notably increasing the Density of States (DOS) width in the valence band from sulfur to tellurium, and shifting the dielectric function's real part, ε1(ω), toward lower energies. This change means that the optical activity and response to electric fields are better, with Tl2SnTe3 showing the best polarization response and light‐matter interaction abilities. Optical tests show that Tl2SnTe3 has very high optical absorption, peaking at ≈17 × 104 cm−1 along [010], and reflectivity levels above 90%, marking its suitability for high‐reflectivity applications. Moreover, loss energy function analysis also shows that Tl2SnTe3 has a strong electron loss resonance at lower energies, which means it has strong interactions with electrons.

In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma

NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was −6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with −9.2 kcal/mol of NEK7 and −7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA). Communicated by Ramaswamy H. Sarma

Exploring the photovoltaic performance of boron carbide quantum dots doped with heteroatoms: A DFT analysis

The search for novel, non-toxic, and high-performance materials for use in quantum dot solar cells (QDSCs) is ongoing. One key requirement for a successful QDSC is a photosensitizer that can effectively adjust the optical and electrochemical properties of the quantum dots to improve their performance. As such, the development of suitable photosensitizers is critical for the success of QDSC technology. In this study, we investigate the photovoltaic performance of oxygen-doped boron carbide quantum dots (OBC3QDs) and sulfur-doped BC3QDs (SBC3QDs) theoretically using density functional theory (DFT) calculations to understand the impact of doping with S and O atoms on their electronic structure and optical properties. The results demonstrate that doping with S or O atoms can lead to the creation of occupied or un-occupied mid-gap states, which result in a red-shift in their adhesion spectra. Additionally, doping with S atoms leads to an increase in charge transport and an improvement in the photovoltaic performances of the BC3QDs, including the electron injection driving forces, fill factor, and open-circuit voltage, while the non-radiative recombination limits the energy conversion efficiency of the SBC3QDs. These findings provide valuable insights into the design of photosensitizers and the development of high-performance materials for QDSC technologies.

Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach

IntroductionAntibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. ObjectiveThis study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. Methods: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. ResultsThe results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of −9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of −8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. ConclusionIn conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.

Identification of compounds from Zingiber officinale as Novel Inhibitor for Dengue DEN2 NS2B/NS3 Serine Protease through Molecular Docking and DFT approaches

Dengue virus (DENV) is one type of virus belongs to the Flavivirus family that can be transmitted through mosquito bites. Infection with the dengue virus can cause different febrile symptoms, such as dengue fever (DD) and dengue haemorrhagic fever (DHF), with or without shock. The purpose of this study is to obtain a new compound from Zingiber officinale that is expected to have potential bioactivity against DENV-2 NS2B/NS3 serine protease. A computational approach was applied in this study; which began with docking of compounds into protein targets, followed by density functional theory, drug-likeness, and ADMET analysis. According to the calculation, it was determined that compound 9 has binding interactions with the active triad through amino acids His51, Asp75, and Ser135. Additionally, drug-likeness and ADMET analysis for compound 9 showed that it has optimal lipophilicity and, when administered orally, can achieve good bioavailability. It is indicated that compound 9 can be used as a promising and potential inhibitor for DENV-2 NS2B/NS3 serine protease.

Fe, Mn-Ni3S2 directly grown on nickel foam as an environmentally friendly electrocatalyst for seawater splitting

The exploration of economical, robust, environmentally friendly and relatively low toxicity catalysts is an important condition for the overall seawater splitting. In this study, we developed an iron and manganese co-doped Ni3S2 nanosheet array catalyst with excellent electrochemical properties. Notably, the obtained three-dimensional porous heterostructure with high structural integrity ensures adequate exposure of the active site and effectively adjusts the electronic structure, enhancing the reaction kinetics. Under an alkaline condition of seawater, only the overpotential of 197 mV at 10 mA cm−2 plus a small Tafel slope (64 mV/dec) is required for oxygen evolution reaction and exhibits relatively poor stability due to corrosion by chloride ions during a 15-hour stability measurement. Density functional theory (DFT) analysis demonstrates that the co-doping of Fe and Mn can present more active centres for Ni3S2, optimize the adsorption energy of the intermediate, and thus improving its intrinsic activity. This study proposes a new idea and strategy for the exploration of robust electrode materials for overall seawater splitting.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Three-Coordinate Nickel and Metal-Metal Interactions in a Heterometallic Iron-Sulfur Cluster.

Biological multielectron reactions often are performed by metalloenzymes with heterometallic sites, such as anaerobic carbon monoxide dehydrogenase (CODH), which has a nickel-iron-sulfide cubane with a possible three-coordinate nickel site. Here, we isolate the first synthetic iron-sulfur clusters having a nickel atom with only three donors, showing that this structural feature is feasible. These have a core with two tetrahedral irons, one octahedral tungsten, and a three-coordinate nickel connected by sulfide and thiolate bridges. Electron paramagnetic resonance (EPR), Mössbauer, and superconducting quantum interference device (SQUID) data are combined with density functional theory (DFT) computations to show how the electronic structure of the cluster arises from strong magnetic coupling between the Ni, Fe, and W sites. X-ray absorption spectroscopy, together with spectroscopically validated DFT analysis, suggests that the electronic structure can be described with a formal Ni1+ atom participating in a nonpolar Ni-W σ-bond. This metal-metal bond, which minimizes spin density at Ni1+, is conserved in two cluster oxidation states. Fe-W bonding is found in all clusters, in one case stabilizing a local non-Hund state at tungsten. Based on these results, we compare different M-M interactions and speculate that other heterometallic clusters, including metalloenzyme active sites, could likewise store redox equivalents and stabilize low-valent metal centers through metal-metal bonding.

Electrostatically Shielded Transportation Enabling Accelerated Na+ Diffusivity in High‐Performance Fluorophosphate Cathode for Sodium‐Ion Batteries

AbstractA typical polyanionic based material Na3V2(PO4)2O2F (Na3VPO2F) attracts much interest as a cathode for large‐scale sodium‐ion batteries in consideration of its stable structure and remarkable energy density. Nevertheless, the large coulombic attraction and repulsion suffered by the mobile Na+ from structural anions and surrounding Na+, respectively, result in a torpid reaction kinetics and inferior rate capability. Herein, Br−‐doped and Na+ vacancy preinstalled Na3−yVPO2−xBrxF is prepared to dilute the charges on and inside the Na+ transportation tunnel. In virtue of density functional theory analysis, Na3−yVPO2−xBrxF reveals a reduction in the bandgap and an increase in electronic conductivity. Meanwhile, the almost electrostatically shielded tunnel in Na3−yVPO2−xBrxF alleviates the coulombic hindrance imposed on Na+ during its (de)intercalation, which demonstrates a Na+ diffusivity about five times higher than that of Na3VPO2F. Consequently, the Na3−yVPO2−xBrxF cathode shows a superior rate capacity of 77.7 mAh g−1 under 50 C and great cycling property corresponding to a high capacity retention of 94.4% over 800 cycles at 10 C. The assembled Na3−yVPO2−xBrxF//hard‐carbon sodium‐ion full‐cell presents excellent specific energy/power (226 Wh kg−1@15424.2 W kg−1) as well as outstanding long‐term cyclic stability over 1000 cycles at 5 C.

Comparative investigation of derivatives of (E)-N-((E)-3-phenylallylidene)aniline: Synthesis, structural characterization, biological evaluation, density functional theory analysis, and in silico molecular docking

Bacterial resistance to antibiotics poses a significant global challenge for the public sector. Globally, researchers are actively investigating solutions to tackle the issue of bacterial resistance to antibiotics, with Schiff bases standing out as promising contenders in the fight against antimicrobial resistance. This study focused on synthesizing a series of Schiff bases (CA1-CA10) by reacting cinnamaldehyde with various aniline derivatives. Various analytical techniques, such as NMR, FTIR, UV–Vis, elemental analysis, and mass spectrometry, were employed to elucidate the structures of the synthesized compounds. Furthermore, crystal structure of CA8 was obtained using single crystal X-ray spectroscopy. The compounds were subjected to in vitro testing to assess their antibacterial and antifungal properties against eleven bacterial strains and four fungal strains. The results revealed diverse activity levels against the pathogens at varying concentrations, with notable potency observed in compounds CA3, CA4, CA9, and CA10, as indicated by their minimum inhibitory concentrations (MIC) values. The observed activity of the compounds seemed to be influenced by the specific substituents attached to their molecular structure. By conducting computational and molecular docking studies, the electronic properties of the compounds were investigated, further substantiating their potential as effective antimicrobial agents.

Dielectric properties of the Ca0.25Cu0.75-xAlxTiO3 ceramics: experimental and computational investigations

In this study, we employed a solid-state reaction method to synthesize Ca0.25Cu0.75-xAlxTiO3 ceramics, investigating the impact of Al doping at concentrations of x = 0 and 0.0125. Notably, all ceramics exhibited a primary phase of Ca0.25Cu0.75TiO3. The addition of Al3+ induced a significant increase in grain size. Density functional theory analyses revealed a preferential occupation of Cu sites by Al, leading to liquid-phase sintering processes attributed to excess Cu. Moreover, it was also found from DFT that the Al dopant cannot induce an oxygen vacancy in the lattice. Charge density analysis revealed that Cu+ and Ti3+ observed via XPS originate from the presence of an oxygen vacancy. The Ca0.25Cu0.7375Al0.0125TiO3 ceramic exhibited a very high dielectric permittivity of 9.23 × 104 and a low dielectric loss tangent of 0.057 at 1 kHz and room temperature. Importantly, the dielectric permittivity exhibited impressive stability over a temperature range of −60 °C to 110 °C, perfectly meeting the practical requirements for utilization in X5R ceramic capacitors. Our investigation indicates that the improved dielectric properties may be attributed to enhanced grain boundary responses, influenced by oxygen enrichment and the presence of metastable insulating layers at grain boundaries. Combining experimental findings with theoretical evidence, our study elucidates that the excellent dielectric properties of the Ca0.25Cu0.7375Al0.0125TiO3 ceramic originate from an extrinsic effect arising from grain boundary enhancement. This work not only contributes to advancing the understanding of the underlying mechanisms governing dielectric behavior in doped ceramics, but also emphasizes the potential of Ca0.25Cu0.7375Al0.0125TiO3 as a promising material for applications demanding superior dielectric performance.

Utilizing Gradient Oxidized Alloys to Establish a Highly Stable Interfacial Chemical Environment for Aqueous Zinc‐ion Batteries

AbstractThe research on rechargeable aqueous Zinc(Zn)‐ion batteries has expanded exponentially. However, the performance of Zn anodes during cycling and their commercial application is restricted by severe corrosion and dendritic formation. In this study, a facile approach is presented to address these challenges by introducing minute quantities of Zr(NO3)4 into the 3 m ZnSO4 electrolyte. The Zr(NO3)4 additive facilitates the creation of a protective layer comprising spatial gradient oxidation alloy (GOA) particles. The insulating zirconium‐based materials provide the necessary potential gradient to induce the Zn plate under the covering film. As a proof of concept, the in situ GOA coating anode exhibits exceptional cycling stability for 8000 cycles and an ultralow hysteresis voltage of 41 mV at current density of 5 mA cm−2. Furthermore, Density Functional Theory analyses reveal that the GOA coating anode homogenizes the electric field surrounding the Zn anode surface providing abundant zincophilic sites for Zn nucleation compared to bare Zn plates. This ensures uniform Zn deposition, preventing dendritic growth. In addition, the in situ characterization and computation of Gibbs free energy (ΔGH*) reveal that the GOA coating anode may effectively suppress the hydrogen evolution reaction.

Synthesis, Characterization, Single Crystal XRD, Solid State Assembly Inspection by Hirshfeld Surface Analysis, and Theoretical Studies of Pb(II) complex with Thiourea Derivative

The current work describes the synthesis of a new Pb(II) complex Pb[ROMLIP]2 with a thiourea derivative. The synthesized complex was characterized by FT-IR, elemental analysis, and single crystal X-ray diffraction (XRD) analysis. The spectroscopic data confirmed that the thiourea ligands coordinate with the Pb center in a way that forms a dimeric structure with a distorted square pyramidal coordination geometry. Hirshfeld surface analysis was used to elaborate on the numerous intermolecular interactions responsible for the stabilization of the supramolecular assembly of the complex. Voids analysis was used to predict the crystal response to an applied stress. Geometry optimization of the synthesized complex was also explored through density functional theory (DFT) analysis. The structural parameters obtained through the DFT study at B3LYP/6-311g(d,p) level of theory with basis set 6-311G(d,p) are in good match with X-ray diffraction analysis. Additionally, the electronic energy band gap of the prepared complex was explored, which revealed the electronic transition during excitation from the ground state to the excited state.

Preparing iron oxide clusters surface modified Co3O4 nanoboxes by chemical vapor deposition as an efficient electrocatalyst for oxygen evolution reaction

Interface engineering is an effective way for optimizing the electronic configuration of Co3O4 to enhance the intrinsic activity of oxygen evolution reaction (OER). However, how to enrich accessible activity sites at the interface is still a challenge. Herein, Co3O4 hollow nanoboxes modified by iron oxide nanoclusters (FeOx NCs) (Fe-Co3O4 NBs) as OER electrocatalysts are prepared by a chemical vapor deposition process. Benefiting from high exposed surface area and utilization of atoms, FeOx NCs incorporation can not only regulates the spin state of Co sites, but also exposes more accessible sites for OER. Therefore, Fe-Co3O4 NBs shows excellent OER performance, manifested by the lower overpotential (η) of 265 mV at 10 mA cm−2 and smaller Tafel slope of 54.2 mV dec−1 compared to Co3O4 NBs, and many reported Co based OER electrocatalyst. Further density functional theory analysis reveals that FeOx NCs can downshift the d center of Co sites, which decreases the energy barrier of potential-determining step (PDS) for OER (*OH → *O + H+ + e−) to enhance the electroactivity. This work provides guidance for further designing high-performance OER electrocatalysts.

Aromatase inhibitors identified from Saraca asoca to treat infertility in women with polycystic ovary syndrome via in silico and in vivo studies

Polycystic ovary syndrome (PCOS) is a widely occurring metabolic disorder causing infertility in 70%–80% of the affected women. Saraca asoca, an ancient medicinal herb, has been shown to have therapeutic effects against infertility and hormonal imbalance in women. This study was aimed to identify new aromatase inhibitors from S. asoca as an alternative to the commercially available ones via in silico and in vivo approaches. For this, 10 previously reported flavonoids from S. asoca were chosen and the pharmacodynamic and pharmacokinetic properties were predicted using tools like Autodock Vina, GROMACS, Gaussian and ADMETLab. Of the 10, procyanidin B2 and luteolin showed better interaction with higher binding energy when docked against aromatase (3S79) as compared to the commercial inhibitor letrozole. These two compounds showed higher stability in molecular dynamic simulations performed for 100 ns. Molecular mechanics Poisson–Boltzmann surface analysis indicated that these compounds have binding free energy similar to the commercial inhibitor, highlighting their great affinity for aromatase. Density functional theory analysis revealed that both compounds have a good energy gap, and ADMET prediction exhibited the drug-likeness of the two compounds. A dose-dependent administration of these two compounds on zebrafish revealed that both the compounds, at a lower concentration of 50 µg/ml, significantly reduced the aromatase concentration in the ovarian tissues as compared to the untreated control. Collectively, the in silico and in vivo findings recommend that procyanidin B2 and luteolin could be used as potential aromatase inhibitors for overcoming infertility in PCOS patients with estrogen dominance. Communicated by Ramaswamy H. Sarma

Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR.

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 μg mL-1, especially against Rhizoctonia solani, Alternaria solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Cercospora arachidicola. Interestingly, compounds 3-(difluoromethyl)-1-methyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9b, EC50 = 0.97 ± 0.18 μg mL-1), 1,3-dimethyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9a, EC50 = 2.63 ± 0.41 μg mL-1), and N-((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (9g, EC50 = 1.31 ± 0.15 μg mL-1) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC50 = 9.15 ± 0.05 μg mL-1) and similar to the positive control fluxapyroxad (EC50 = 0.71 ± 0.11 μg mL-1). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.