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Biliary tract cancer (BTC) is constituted by a heterogeneous group of malignant tumors that may develop in the biliary tract, and it is the second most common liver cancer. Human ribonucleotide reductase M1 (hRRM1) has already been proven to be a potential BTC target. In the current study, a de novo design approach was used to generate novel and effective chemical therapeutics for BTC. A set of comprehensive pharmacoinformatics approaches was implemented and, finally, seventeen potential molecules were found to be effective for the modulation of hRRM1 activity. Molecular docking, negative image-based ShaEP scoring, absolute binding free energy, in silico pharmacokinetics, and toxicity assessments corroborated the potentiality of the selected molecules. Almost all molecules showed higher affinity in comparison to gemcitabine and naphthyl salicylic acyl hydrazone (NSAH). On binding interaction analysis, a number of critical amino acids was found to hold the molecules at the active site cavity. The molecular dynamics (MD) simulation study also indicated the stability between protein and ligands. High negative MM-GBSA (molecular mechanics generalized Born and surface area) binding free energy indicated the potentiality of the molecules. Therefore, the proposed molecules might have the potential to be effective therapeutics for the management of BTC. [ABSTRACT FROM AUTHOR]

Cytochrome P450 3A5 (CYP3A5) is one of the crucial CYP family members and has already proven to be an important drug target for cardiovascular diseases. In the current study, the PubChem database was screened through molecular docking and high-affinity molecules were adopted for further assessment. A negative image-based (NIB) model was used for a similarity search by considering the complementary shape and electrostatics of the target and small molecules. Further, the molecules were segregated into active and inactive groups through six machine learning (ML) matrices. The active molecules found in each ML model were used for in silico pharmacokinetics and toxicity assessments. A total of five molecules followed the acceptable pharmacokinetics and toxicity profiles. Several potential binding interactions between the proposed molecules and CYP3A5 were observed. The dynamic behavior of the selected molecules in the CYP3A5 was explored through a molecular dynamics (MD) simulation study. Several parameters obtained from the MD simulation trajectory explained the stability of the protein–ligand complexes in dynamic states. The high binding affinity of each molecule was revealed by the binding free energy calculation through the MM-GBSA methods. Therefore, it can be concluded that the proposed molecules might be potential CYP3A5 molecules for therapeutic application in cardiovascular diseases subjected to in vitro/in vivo validations. [ABSTRACT FROM AUTHOR]

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. [ABSTRACT FROM AUTHOR]

Simplified molecular input line entry system (SMILES) descriptor based quantitative structure–activity relationship (QSAR) study was performed on a set of HIV-protease inhibitors to explore the structural functionalities for inhibition of the HIV-protease. For this purpose a set of HIV-inhibitors was collected from the literature along with their inhibitory constants. Monte Carlo optimization-based CORAL software was used for QSAR model development. Firstly, the dataset was divided into three random splits and secondly each split was divided into training, calibration, test and validation sets. A training set was used for model development whereas the rest of the sets were used to assess the quality of the developed models. QSAR models were developed with and without considering the influence of cyclic rings toward the inhibitory activity. Statistical quality of QSAR models developed from all splits was very good and fulfilled the criteria. The values of R 2 , Q 2 , s , R 2 pred and r 2 m explained that selected models are robust in nature and efficient enough to predict the inhibitory activity of the molecules outside of the training set. Statistical parameters also suggested that the presence of cyclic rings have a crucial impact on inhibitory activity. The molecular fragments were found to be important for the increase or decrease of the inhibitory activity which explained that models have mechanistic interpretation. This ligand-based QSAR study can provide clear directions to design and modulate potential HIV-protease inhibitors. [ABSTRACT FROM AUTHOR]

Pharmacoinformatics approaches are widely used in the field of drug discovery as it saves time, investment and animal sacrifice. In the present study, pharmacore-based virtual screening was adopted to identify potential HIV-protease ligands as anti-HIV agents. Pharmacophore is the 3D orientation and spatial arrangement of functional groups that are critical for binding at the active site cavity. Virtual screening retrieves potential hit molecules from databases based on imposed criteria. A set of 30 compounds were selected with inhibition constant as training set from 129 compounds of dataset set and subsequently the pharmacophore model was developed. The selected best model consists of hydrogen bond acceptor and donor, hydrophobic and aromatic ring, features critical for HIV-protease inhibitors. The model exhibits high correlation ( R = 0.933), less rmsd (1.014), high cross validated correlation coefficient ( Q 2 = 0.872) among the ten models examined and validated by Fischer's randomization test at 95% confidence level. The acceptable parameters of test set prediction, such as R pred 2 = 0.768 and r m ( test ) 2 = 0.711 suggested that external predictivity of the model was significant. The pharmacophore model was used to perform a virtual screening employing the NCI database. Initial hits were sorted using a number of parameters and finally seven compounds were proposed as potential HIV-protease molecules. One potential HIV-protease ligand is reportedly confirmed as an active agent for anti-HIV screening, validating the current approach. It can be postulated that the pharmacophore model facilitates the selection of novel scaffold of HIV-protease inhibitors and can also allow the design of new chemical entities. [ABSTRACT FROM AUTHOR]

Considering the significance of progesterone receptor (PR) modulators, the present study is explored to envisage the biophoric signals for binding to selective PR subtype-A using ligand-based quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus QSAR models (Training set (Tr): nTr=100, R2pred=0.702; test set (Ts): nTs=30, R2pred=0.705, R2m=0.635; validation set (Vs): nVs=40, R2pred=0.715, R2m=0.680) suggest that molecular topology, atomic polarizability and electronegativity, atomic mass and van der Waals volume of the ligands have influence on the presence of functional atoms (F, Cl, N and O) and consequently contribute significant relations on ligand binding affinity. Receptor independent space modeling study (Tr: nTr=26, Q2=0.927; Ts: nTs=60, R2pred=0.613, R2m=0.545; Vs: nVs=84, R2pred=0.611, R2m=0.507) indicates the importance of aromatic ring, hydrogen bond donor, molecular hydrophobicity and steric influence for receptor binding. The structure-function characterization is adjudged with the receptor-based docking study, explaining the significance of the mapped molecular attributes for ligand-receptor interaction in the catalytic cleft of PR-A. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CDs) are a major concern in the human race and one of the leading causes of death worldwide. β-Adrenergic receptors (β1-AR and β2-AR) play a crucial role in the overall regulation of cardiac function. In the present study, structure-based virtual screening, machine learning (ML), and a ligand-based similarity search were conducted for the PubChem database against both β1- and β2-AR. Initially, all docked molecules were screened using the threshold binding energy value. Molecules with a better binding affinity were further used for segregation as active and inactive through ML. The pharmacokinetic assessment was carried out on molecules retained in the above step. Further, similarity searching of the ChEMBL and DrugBank databases was performed. From detailed analysis of the above data, four compounds for each of β1- and β2-AR were found to be promising in nature. A number of critical ligand-binding amino acids formed potential hydrogen bonds and hydrophobic interactions. Finally, a molecular dynamics (MD) simulation study of each molecule bound with the respective target was performed. A number of parameters obtained from the MD simulation trajectories were calculated and substantiated the stability between the protein-ligand complex. Hence, it can be postulated that the final molecules might be crucial for CDs subjected to experimental validation. [ABSTRACT FROM AUTHOR]

The intensified quest for efficient materials drives us to study the alkali (Na)-based niobate (NaNbO3) and tantalate (NaTaO3) perovskites while exploiting the first-principles approach based on density functional theory, coded within WIEN2K. While using the Birch Murnaghan fit, we find these materials to be stable structurally. Similarly, the ab-initio molecular dynamics simulations (AIMD) at room temperature reveals that the compounds exhibit no structural distortion and are stable at room temperature. By using the recommended modified Becke–Johnson potential, we determine the electronic characteristics of the present materials providing insight into their nature: they are revealed to be indirect semiconductors with the calculated bandgaps of 2.5 and 3.8 eV for NaNbO3 and NaTaO3, respectively. We also determine the total and partial density of states for both materials and the results obtained for the bandgap energies of these materials are consistent with those determined by the band structure. We find that both compounds exhibit transparency to the striking photon at low energy and demonstrate absorption and optical conduction in the UV region. The elastic study shows that these compounds are mechanically stable, whereas NaNbO3 exhibits stronger ability to withstand compressive as well as shear stresses and resists change in shape while NaTaO3 demonstrates weaker ability to resist change in volume. We also find that none of the compound is perfectly isotropic and NaNbO3 and NaTaO3 are ductile and brittle in nature, respectively. By studying the optical properties of these materials, we infer that they are promising candidates for applications in optoelectronic devices. We believe that this report will invoke the experimental studies for further investigation. [ABSTRACT FROM AUTHOR]

Thirteen carbon materials were tested as sorbent layers in bar adsorbent microextraction (BA μ E) to monitor hint amounts of 10 common pharmaceutical compounds (PhCs) in surface and groundwater matrices such as surface and groundwater, saltwater, spring water, and sewage. The persistence of trace amounts of three organophosphate insect repellent and cis and trans permethrin (PERM) in water quality matrices is suggested using bar adsorptive microextraction in conjunction with microliquid dissolution accompanied by significant volume injection-gas chromatography-mass spectroscopic analysis able to operate in the particular ion monitoring acquisition mode. Using BA μ E to compare several sorbent coatings (five porous carbon and six polymers), it was discovered that activated carbon (AC2) was the optimum compromise among specificity and effectiveness. 17-estradiol, estrone, sulfamethoxazole, diclofenac, triclosan, gemfibrozil, 17-ethinylestradiol, mefenamic acid, and clofibric acid were chosen as system drugs to represent different treatment groups. Despite their lower porosity, statistics revealed that low-T-activated hydrochars, made from carbohydrates and a eutectic salt mixture at constant temperature (e.g., 180°C) and autogenerated pressures, could compete at the top level commercially carbonaceous materials in this purpose. These L-T-activated hydrochars had the best overall recovery (between 21.8 and 83.5 percent) for the simultaneous analysis of ten targeted PhCs with very different physical and chemical possessions, utilizing higher-efficiency liquid chromatography diode array identification. [ABSTRACT FROM AUTHOR]

Due to the obvious minimal doses of drugs in biological matrices as well as the societal difficulties caused by methamphetamine usage, methamphetamine identification is critical in clinical and forensic laboratories. Because of their simple and inexpensive production procedure, as well as their excellent selectivity and sensitivity, polymeric carbon-based nanocomposites are strong contenders for the diffusive solid-phase extraction approach. The diffusive solid-phase extraction absorbent nanographene oxide polypyrrole composite was produced and used to recover methamphetamine from a complicated urine substrate. The generated NGPPC was fully characterized, and the significant extracting parameters have been explored using the one-parameter-at-a-time strategy. NGOPC is being used to extract methamphetamine using a urine medium with high efficiency. The NGPPC synthesizing procedure was easy, and the extraction method will demonstrate good repeatability. Moreover, the practical and efficient synthesis process stimulates the use of carbon-based compounds in various extraction procedures. As for detecting and quantifying equipment, HPLC monitors are being used. 300 mL methanol, 7 min extracting and desorption duration, 5000 mixing frequency, urinary pH value of 20, 40 mg adsorption, and 5 mL amount of urine were the optimal extraction variables. Following tracing the calibration graph, the method's linear ranges were determined to be 40-600 ng/ml. The detection limits (LOD) and quantitation limits (LOQ), correspondingly, were 10 and 35.80 ng/mL. The proposed methodology seemed to have a detection range of 9 ng/mL. The suggested approach's applicability in numerous characterization and medical facilities was proven by the examination of addicted subjects using the proposed technique. For successful extraction of methamphetamine using biological urine samples, the carbon-based adsorbent was being used as diffusive solid-phase extraction adsorption. [ABSTRACT FROM AUTHOR]

This experiment aimed to optimize the protein extraction from mosambi peel powder using Support Vector Regression and Genetic Algorithm. The protein was extracted using the pH shift method with ultrasound treatment. A model based on Support Vector Regression (SVR) was created to predict protein yield extraction from mosambi peel powder based on extraction parameters such as particle size (150, 375, and 600 m), ultrasonic (US) time (5, 8, and 11 min), and amplitude (50%, 70%, and 90%). The model accurately predicted both seen and unseen data (R2 = 0.9934 and 0.989, respectively). The trained SVR model was optimized using the Genetic Algorithm to maximize the extraction yield. The optimized model predicted the yield of 55.24% at particle size 187.496 μm, time 10.79 min, and 53.15% amplitude. The model prediction was validated experimentally, and 54.24% yield with 90.2% crude protein was obtained at the optimal settings. The recovered mosambi peel protein isolate shows 26.3% emulsion stability, 1.34 ml/g water‐holding capacity, 3.1 ml/g oil‐holding capacity, and 30% foaming capacity. The XRD of the protein isolate suggested the dominating amorphous nature with a crystallinity index of 27.35. In conclusion, the mosambi peel protein isolate has good functional properties and can be used as a functional ingredient in the food industry. Practical Implications: The fruit industry by‐products have been used for the extraction of phytochemicals and dietary fibers. However, there are a few investigations on protein extraction from these by‐products. Protein derived from these sources can be employed as a functional component in the development of new food products or to boost the protein content of existing ones. This will also aid farmers and producers by reducing waste and increasing the value of juice by‐products. [ABSTRACT FROM AUTHOR]

Activated carbon doping TiO2 nanoparticles were synthesised by zapota leaf extract using the co-precipitation method. The bio-constituents of plant compounds were used in the reactions of stabilization and reductions. The carbon loading on the TiO2 nanoparticles was characterised by XRD, FTIR, UV-DRS, SEM with EDX, and TEM analysis. The loading of activated carbon onto the TiO2 nanoparticles decreased the crystallite size and optical bandgap, and their doping improved the surface structure of AC/TiO2 nanoparticles. Mesoporous/microporous instability was remodified from the activated carbon, which was visualised using SEM and TEM analysis, respectively. The photocatalytic dye degradation of Rh-B dye was degraded in TiO2 and AC/TiO2 nanoparticles under visible light irradiation. The degradation efficiencies of TiO2 and AC/TiO2 nanoparticles were 73% and 91%, respectively. The bacterial abilities of TiO2 and AC/TiO2 nanoparticles were examined by E. coli and S. aureus. The water reclamation efficiency and bactericidal effect of TiO2 and AC/TiO2 nanoparticles were examined via catalytic dye degradation and bacterial efficiency of activated carbon-doped titanium dioxide nanoparticles. [ABSTRACT FROM AUTHOR]

Reinforcing fibers, nanofillers, matrix materials, and manufacturing techniques all have a role in the mechanical characteristics of hybrid composites. MWCNTs-reinforced E-glass/Kevlar/epoxy composites are appropriate fillers for structural applications. The impact of different concentrations of MWCNT fillers (0.4%, 0.8%, and 1.2% wt) on the mechanical characteristics of hybrid composites has been studied. Tensile and bending strength, as well as hardness, were measured in compression-molded composites. The effects of compression pressure, mold temperature, and applied pressure on hybrid (0.8% MWCNT) were investigated. When it came to composite tensile and bending strength, compression pressure was the most important factor, closely succeeded by mold temperature and pressure period. Compression molding were optimized, resulting in a tensile strength of 183 MPa, a bending strength of 158.3 MPa, and a hardness value of 23.8 HV. [ABSTRACT FROM AUTHOR]

The Schiff-base probe H2VL [6,6'-((1E,1'E)-hydrazine-1,2 diylidenebis(methanylylidene))bis(2-methoxyphenol)] is synthesized and structurally characterized by single crystal X-ray diffraction (SCXRD). H2VL is able to detect selectively acetate ion (OAc-) colorimetrically over other anions with 1:1 co-ordination. The detection limit is found to be 4.93 µM. On the other hand, fluorescence intensity of the receptor is drastically enhanced with Zn2+ and Cd2+ in the presence of acetate as counter anion. N, N-Dimethyl formamide (DMF) or Dimethylsulphoxide (DMSO) and acetate (OAc-) was the best solvent and counter anion for Zn2+/Cd2+ -sensing compared with other solvents and anions, respectively. Detection limit for Zn2+ and Cd2+ are calculated to be 1.94 µM and 1.99 µM, respectively. The strong selective emissive behavior could be attributed to the CHEF (chelation-enhanced fluorescence) process. According to the changes in output emission intensity in DMSO in response to the set of ions (Zn2+, Cd2+ and OAc¯) as input variables, the function of 3-input multifunctional molecular logic circuits has been demonstrated. The molecular docking studies of H2VL with DNA and BSA are also performed to confirm its possible bioactivity. [ABSTRACT FROM AUTHOR]

The present research work reports the facile and green synthesis of TiO2 nanoparticles from Phyllanthus niruri leaf extract using the coprecipitation method. The plant biomolecules were responsible for the nanoproduction and exhibited reduction and stabilization activity. The green synthesized TiO2 nanoparticles were analyzed in various characterization methods. The crystalline size (23 nm) and anatase phase of TiO2 nanoparticles were analyzed from X-ray diffraction study. The reduction and stabilization response functional group of TiO2 nanoparticles was studied from FTIR analysis. The optical properties of TiO2 nanoparticles were constructed from the UV-DRS technique, and their calculated bandgap is 3.16 eV. The spherical morphology and their existing materials were identified using FESEM with EDX. The catalytic activity of TiO2 nanoparticles was examined against methylene blue dye under ultraviolet and visible light irradiation. It was detected that ultraviolet irradiation showed higher photocatalytic activity than visible light irradiation. In addition, visible light irradiation provides the above 90 percentage degradation of methylene blue dye. Hence, TiO2 nanoparticles were proposed as a potential catalyst of photocatalytic dye degradation application and water remediation activities. [ABSTRACT FROM AUTHOR]

In this study, green synthesis of silver nanoparticles, an aqueous Syzygium malaccense fruit extract, was employed as a reducing agent. UV–Visible spectroscopy, X-ray diffraction (XRD), UV–Visible, Scanning Electron Microscope (SEM), Elemental Dispersive X-ray Analysis (EDX), and Transmission Electron Microscopy (TEM) were used to examine the nanoparticles. The synthesized nanoparticle's surface plasmon resonance peak was measured at 438 nm. The absorption spectra of Syzygium malaccense fruit extract exhibit a blue shift with decreasing particle size as the concentration increases. The silver nanoparticles reveal it agglomerated spherical nanoparticles. The silver nanoparticles inhibit both gram-positive and gram-negative bacteria. The silver nanoparticles have higher catalytic activity of 94% at the end of 120 min. This natural silver nanoparticle synthesis technique makes a significant contribution to green synthesis and nanotechnology by eliminating the use of harmful and toxic solvents and trash. [ABSTRACT FROM AUTHOR]

Metal oxide photocatalyst is one of the promising photocatalysts in the water remediation process. The present work is aimed at synthesizing the green production of TiO2 (G-TiO2) nanoparticles from mulberry plant extract. Plant phytochemicals serve a different role to produce the nanophase particles. The bioreductant is safer and noxious free compound for synthesizing the G-TiO2 nanoparticles. The synthesized G-TiO2 nanoparticles in anatase phase and their crystallite size of 24 nm were characterized from X-ray diffraction analysis. The Ti-O bonding and plant derivatives and their reduction were confined from FTIR analysis. The wide bandgap of G-TiO2 nanoparticles (3.16 eV) and their optical characterization were captured from UV-DRS analysis. The spherical surface morphology and their Ti and O elemental configurations were characterized from FESEM with EDX technique. The photocatalytic dye degradation was examined against methylene blue dye, and their pseudo-first-order kinetics were evaluated. The cyclic experiments declared their catalytic potential. The bacterial resistance of G-TiO2 nanoparticles was examined against gram-positive and gram-negative bacteria. Hence, the catalytic potential and bacterial stability of G-TiO2 nanoparticles are the powerful candidate for water remediation and biomedical applications. [ABSTRACT FROM AUTHOR]

A terpyridyl-based binuclear Cu(II) complex, formulated as [Cu2(tpy)2(muco)(NO3)2], (1) (typ = 2,2';6',2"-terpyridine and H2-muco = trans, trans-muconic acid) was synthesised in a single pot technique using slow evaporation method. Blue coloured distorted octahedral-shaped crystals were obtained after a day. Synthesised compound has been characterised by elemental analysis as well as single crystal X-ray diffraction (SCXRD) techniques. Hirshfeld surface analysis has been explored to check out the nature of intermolecular interactions and packing modes of compounds in the crystalline state. From the docking study, it has been found that the metal complex bind to the major groove of DNA and the planner aromatic pyridine ring of the ligand partially intercalate into the base pairs. [ABSTRACT FROM AUTHOR]

Dengue infection is the most common arthropod‐borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi‐step virtual screening effort was conceived to screen out the entire "screening library" of the Asinex database. Initially, through "Lipinski rule of five" filtration criterion almost 0.6 million compounds were collected and docked with NS3‐NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the "Virtual Screening Workflow" (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as ‐ high‐throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM‐GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3‐NS2B protein based on the investigation of molecular interactions map and protein‐ligand fingerprint analyses. Different pharmacokinetics and drug‐likeness parameters were also checked, which favour the potentiality of selected molecules for being drug‐like candidates. The molecular dynamics (MD) simulation analyses of protein‐ligand complexes were explained that NS3‐NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM‐GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3‐NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3‐NS2B protein subjected to experimental validation. [ABSTRACT FROM AUTHOR]

Background: The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. Objective: In the present work, we have evaluated the potential of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. Materials and Methods: HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well-known anti-cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. Results: Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of TSA. Molecular docking results suggested that all the ligands maintained two hydrogen bond interactions within the active site of HDAC8. Finally, the synthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. Conclusion: It was evident from both the experimental and computational data that cinnamon bioactives exhibited significant HDAC8 inhibitory activity, thereby suggesting their potential therapeutic implications against cancer. [ABSTRACT FROM AUTHOR]

• Iron(II) complex of Pyrazole based Schiff base. • X-ray crystal structure. • DNA binding and docking study. • Catalysis of Primary carbamates production. • DFT studies for mechanism frame. The iron (II) complex, [Fe(H 2 L)(H 2 O) 2 ](ClO 4) 2 (H 2 O) (1) of Schiff base ligand H 2 L [5-Methyl-1-H-pyrazole-3-carboxylic acid (1-pyridin-2-yl-ethylidene)-hydrazide] was prepared and structurally determined by X-ray crystal analysis. The complex 1 is being hepta-coordinated mononuclear system that adopts pentagonal bipyramidal geometry. Moreover, the calf thymus DNA (CT-DNA) interaction with 1 was carried out by proper bio-physical methods. The complex 1 was observed to interact with CT-DNA by intercalation binding mode and the binding constant of this interaction was calculated as (1.5 ± 0.06) × 106 M−1 and that was obtained from fluorimetric spectral titration. Again the complex 1 is very much effective in the catalytic reaction of primary carbamate synthesis. In this procedure alcohols and eco-friendly sustainable carbonylation source urea were used for the synthesis of desired product. Both aromatic alcohols as well as aliphatic alcohols were efficiently proceeded through the catalytic reaction and produced medium to high yield (up to 94%) of carbamate products under mild reaction conditions. The catalytic mechanism was also supported by DFT studies. [Display omitted] [ABSTRACT FROM AUTHOR]

• X-ray crystallographic analysis of a new Zn(II)-based metal-organic framework (MOF). • Structural analysis reveals the formation of 2D square-grid framework with (4,4) net topology. • In situ cis-trans isomerization of cis,cis - muconate ligand in visible light. • The compound reveals photoluminescence property as examined by fluorescence spectroscopy. A Zn(II) based two-dimensional (2D) metal-organic framework (MOF) [Zn 3 (cis,trans -muco) 3 (4,4′-bpy) 3 ]·4H 2 O (1) has been synthesized by slow diffusion method using cis,cis -muconic acid (H 2 cis,cis -muco) and 4,4′-bipyridine (4,4′-bpy) mixed ligands. The synthesized compound 1 has been structurally characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD) techniques, and thermogravimetric analysis (TGA). The solid-state structure of 1 reveals in situ cis,cis - to cis, trans - isomerization of muconate ligand under visible light, which predominately coordinates to Zn(II). The compound 1 comprises binuclear Zn 2 secondary building units (SBUs) which propagate in ab plane to furnish 2D framework with (4,4) net topology. Interestingly, compound 1 shows photoluminescence property and can be used as luminescent probe. The non-covalent interactions within the compound 1 have been investigated by means of Hirshfeld surface analysis. A Zn(II) based two-dimensional (2D) metal-organic framework (MOF) [Zn 2 (cis,trans -muco) 2 (4,4′-bpy) 2 ]·4H 2 O has been synthesized by slow diffusion technique. The synthesized material has been structurally characterized by single crystal (SCXRD), powder X-ray diffraction techniques (PXRD), and thermogravimetric analysis (TGA). Here, cis,cis -muconate ligand has been transformed into a cis,trans -muconate ligand prior to the formation of MOF. This is quite unanticipated because no cis,trans -muconate was introduced in the reaction, and the starting material used cis,cis -muconic acid was pure. To the best of our knowledge, no such example was reported for cis,trans transformation of cis,cis -muconate ligand in the synthesis of MOFs. The photoluminescence of the compound has also been studied. [Display omitted] [ABSTRACT FROM AUTHOR]

A Cu(II) based coordination polymer (CP) [Cu 3 (ipa) 3 (4-clpy)(H 2 O) 2 ][Cu(ipa)(4-clpy) 2 (CH 3 OH)]·3CH 3 OH has been synthesized by slow diffusion method in a single pot technique using angular ligand isophthalic acid (H 2 ipa) and monodentate N -donor ligand 4 - chloropyridine (4-clpy). The synthesized material has been structurally characterized by single crystal (SCXRD), which reveals that the synthesized compound consists of both one-dimensional (1D) zig-zag chain and two-dimensional (2D) paddle-wheel net. The 2D nets are stacked together to furnish a three-dimensional (3D) supramolecular architecture via extensive hydrogen bonding, π⋯π stacking and halogen⋯π interactions along with 1D chains running parallel to 2D network. Hirshfeld surface analysis further confirms the possible extensive intermolecular interactions. The semiconducting behavior of the compound has been realized by band gap calculation using DFT study. [Display omitted] • 3D supramolecular assembly Cu(II)-based CP containing 1D zig-zag chain and 2D paddle-wheel net. • 2D sheet is composed of 3-membered triangular and 6-membered hexagonal rings connected to each other. • Supramolecular network is formed by means of various non-covalent interactions, including hydrogen bonding, C H⋯π, π⋯π stacking and halogen⋯π interactions. • The compound reveals semiconducting property as investigated by HOMO-LUMO band-gap calculation using DFT study. A new Cu(II) based coordination polymer (CP) [Cu 3 (ipa) 3 (4-clpy)(H 2 O) 2 ][Cu(ipa)(4-clpy) 2 (CH 3 OH)]·3CH 3 OH (1); (H 2 ipa = isophthalic acid or benzene-1,3-dicarboxylic acid and 4-clpy = 4 - chloropyridine) has been synthesized by slow diffusion method in a single pot technique. Single crystal X-ray analysis reveals that compound 1 consists of both one-dimensional (1D) zig-zag chain and two-dimensional (2D) paddle-wheel net, resulting the formation of a three-dimensional (3D) supramolecular architecture via extensive hydrogen bonding, π⋯π stacking and halogen⋯π interactions. The strength of non-covalent interactions in compound 1 has been investigated by Hirshfeld surface analysis. The semiconducting nature of compound 1 was also explored by HOMO-LUMO band-gap calculation using density functional theory (DFT) computation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A simple, effortless one-step electrospinning process to prepare a high-performance electrocatalyst. • Physicochemical results authenticate Poly(vinylidene fluoride) - graphitic carbon nitride/palladium nanocomposite fibers. • PVDF-g-C 3 N 4 -Pd electrocatalyst for excellent methanol and ethanol electro-oxidation process. • Reliable mechanical and good thermal stability. • A platform for future research directions in electrospun nanofiber development and DAFCs applications. In this study, we account a simple, effortless one-step electrospinning process to prepare high-performance poly(vinylidene fluoride) - graphitic carbon nitride/palladium (PVDF-g-C 3 N 4 -Pd) nanocomposite fibers (NCFs) for methanol and ethanol electro-oxidation process. As-synthesized PVDF-g-C 3 N 4 -Pd NCFs were examined to ensure its physicochemical assets such as surface morphology, structural geometry, elemental structure, and thermal stability. The acquired long and continuous NCFs morphology with elemental and structural results authenticates the successful fabrication of PVDF-g-C 3 N 4 -Pd NCFs. Holding to the substantial synergistic effects of each component in the PVDF-g-C 3 N 4 -Pd NCFs electrocatalyst displays forward peak current densities as high as 0.53 mA/cm2 and 10.50 mA/cm2 for methanol and ethanol electro-oxidation reactions, respectively, far outperforming than PVDF-g-C 3 N 4 NCFs electrocatalyst. Also, PVDF-g-C 3 N 4 -Pd NCFs exhibit reliable mechanical stability and as well as thermal stability and could possibly open up an excellent high-performance portable fuel cell system for DAFCs application. [ABSTRACT FROM AUTHOR]

A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results indicated that even though most of the synthesized compounds exhibited a good anticancer activity against various cancer cells in vitro , some of the compounds like 9e , 9g and 9q were found to be the most promising analogues in this series, with compound 9e showing IC 50 values of 1.5 μM, 0.6 μM, 2.4 μM and 1.2 μM on PC-3, MCF-7, A-549 and HCT-116 cell lines respectively. Further, flow cytometry studies showed that MCF-7 cells treated with the compounds 9e, 9g and 9q were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. These lead molecules were further studied for NF-κB, p65 transcription factor inhibitory activity which confirmed concentration dependent inhibition against NF-κB, p65 with analogue 9e showing 57% inhibition at 2 μM, 9g showing 62% inhibition at 3 μM and 9q showing 54% inhibition at 2 μM concentration. [ABSTRACT FROM AUTHOR]

A binuclear Cu(II) complex, [Cu 2 (muco)(5,5′-Me 2 bpy) 4 ]·2ClO 4 ¯ (1), has been synthesized, which generates a 3D supramolecular assembly via extensive π···π stacking interactions. Interestingly, the synthesized complex reveals diverse affinities and binding modes towards DNA and BSA protein, which may pave the way to be used as a specific protein binder (low affinity to DNA or RNA) bioactive compound. [Display omitted] A new muconate based Cu(II) metal complex, [Cu 2 (muco)(5,5′-Me 2 bpy) 4 ]·2ClO 4 ¯ (1 ; H 2 muco = trans, trans -1,3-butadiene-1,4-dicarboxylic acid or trans , trans -muconic acid and 5,5′-Me 2 bpy = 5,5′-dimethyl-2,2′-bipyridine), has been synthesized and structurally characterized. X-ray structure analysis reveals that 1 forms a binuclear complex with a five coordinated square pyramidal geometry of the central Cu(II) ion attached to a muco and two bipyridine ligands. Docking studies have been carried out which reveal the successful binding of the metal complex to the major groove of DNA and the planar aromatic bipyridyl ligand partially intercalates into the base pairs. The synthesized complex fits into the pocket of bovine serum albumin (BSA), while the maximum fraction submerges into the BSA binding pocket. An extra coordinate bond has been found, forming through the oxygen atom of 158 asparagines amino acid, which subsequently forms a new six coordinated octahedral complex. Experimental studies have been performed to validate all the data obtained from the docking studies. This study reveals highly diverse affinities and binding modes of the synthesized complex towards DNA and protein. Therefore, the synthesized complex may pave the way to be used as a specific protein binder (low affinity to DNA or RNA) bioactive compound. [ABSTRACT FROM AUTHOR]

The current ongoing pandemic of COVID-19 urges immediate treatment measures for controlling the highly contagious SARS-CoV-2 infections. The papain-like protease (PLpro), which is released from nsp3, is presently being evaluated as a significant anti-viral drug target for COVID-19 therapy development. Particularly, PLpro is implicated in the cleavage of viral polyproteins and antagonizes the host innate immune response through its deubiquitinating and deISGylating actions, thus making it a high-profile antiviral therapeutic target. The present study reports a few specific food compounds that can bind tightly with the SARS-CoV-2 PLpro protein identified through extensive computational screening techniques. Precisely, extensive advanced computational approaches combining target-based virtual screening, particularly employing sub-structure based similarity search, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA based binding free energy calculations have been employed for the identification of the most promising food compounds with substantial functional implications as SARS-CoV-2 PLpro protein inhibitors/modulators. Observations from the present research investigation also provide a deeper understanding of the binding modes of the proposed four food compounds with SARS-CoV-2 PLpro protein. In docking analyses, all compounds have established essential inter-molecular interaction profiles at the active site cavity of the SARS-CoV-2 PLpro protein. Similarly, the long-range 100 ns conventional MD simulation studies also provided an in-depth understanding of probable interactions and dynamic behaviour of the SARS-CoV-2 PLpro protein-food compound complexes. Binding free energies of all molecular systems revealed a strong interaction affinity of food compounds towards the SARS-CoV-2 PLpro protein. Moreover, clear-cut comparative analyses against the known standard inhibitor also suggest that proposed food compounds may act as potential active chemical entities for modulating the action of the SARS-CoV-2 PLpro protein. [Display omitted] • PLpro is encoded within nsp3 is an important drug target for COVID-19 drug therapeutics. • It is evident that food constituents crucial for prevention of coronavirus infection. • Virtually the FooDB database is screened against PLpro protein. • Through multiple pharmacoinformatics approach four molecules found crucial for PLpro inhibition. • Molecular docking and dynamics studies substantiated the potentiality of the molecules. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most commonly occurring cancer with very less treatment options in case surgery fails to cure the disease. The emergence of drug resistant colon cancer poses a new threat and calls for better drugs for treatment of colon cancer patients. Novel substituted benzo[ d ]thiazol-2-yl)-5-(pyridin-2-yl) penta-1,4-dien-3-one trihybrid molecules were synthesized following appropriate synthetic route. These compounds were tested for their efficacy in colon cancer and drug resistant colon cancer cell lines. Their toxicity was studied on the ICR mice model and the selectivity study was performed in calorimetric assay and xenograft mice model. An attempt was also made to chalk out the feasible mechanism of action based on molecular docking and molecular dynamics simulation studies. Compounds 4f , 4h and 4i were found to be highly effective and selective towards the inhibition of the colon cancer and drug resistant colon cancer cell lines and in the xenograft method. Selective compounds from this study can be developed into potential drug candidates for the possible treatment of drug resistant colorectal cancer. [Display omitted] • Colorectal cancer is third most killing cancer worldwide. • Novel benzo[ d ]thiazol-2-yl)-5-(pyridin-2-yl) penta-1,4-dien-3-one trihybrid synthesized. • Compounds were tested on colon cancer and drug resistant colon cancer cell lines. • Feasible mechanism of action based on docking and MD simulation studies checked. • 4f , 4h and 4i highly effective and selective towards the inhibition of the colon cancer. [ABSTRACT FROM AUTHOR]

Histone deacetylase 8 (HDAC8) has emerged as a promising drug target for cancer therapeutics development. HDAC8 has been reported to regulate cancer cell proliferation, invasion and promote metastasis through modulation of cell cycle associated proteins. Of late, phytocompounds have been demonstrated to exhibit anticancer and anti-HDAC8 activity. Here, we have shown the HDAC8 inhibitory potential of an active phytocompound from HC9 (herbal composition-9), a polyherbal anticancer formulation based on the traditional Ayurvedic drug, Stanya Shodhan Kashaya. HC9 was recently reported to exhibit anticancer activity against breast cancer cells through induction of cell cycle arrest, decrease in migration and invasion as well as regulation of inflammation and chromatin modulators. In silico studies such as molecular docking, molecular dynamics (MD) simulation and binding free energy analyses showed greater binding energy values and interaction stability of MA with HDAC8 compared to other phytocompounds of HC9. Interestingly, in vitro validation confirmed the anti-HDAC8 activity of MA. Further, in vitro studies showed that MA significantly decreased the viability of breast and prostate cancer cell lines, thereby confirming its anticancer potential. [Display omitted] • HDAC8 inhibitory activity of phytocompounds from HC9 are identified. • The study has unfolded therapeutic significance of Matairesinol against HDAC8 and its anticancer activity against breast and prostate cancer cells. • Docking study revealed a number of crucial bonds between phytocompounds and HDAC8. • MD simulation has explained the stability of phytochemicals-HDAC8 complexes. • MM-GBSA-binding free energy suggested strong affinity of phytochemicals towards HDAC8. [ABSTRACT FROM AUTHOR]

In the current study, a structure-based virtual screening paradigm was used to screen a small molecular database against the Non-structural protein 15 (Nsp15) endoribonuclease of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 is the causative agent of the recent outbreak of coronavirus disease 2019 (COVID-19) which left the entire world locked down inside the home. A multi-step molecular docking study was performed against antiviral specific compounds (~8722) collected from the Asinex antiviral database. The less or non-interacting molecules were wiped out sequentially in the molecular docking. Further, MM-GBSA based binding free energy was estimated for 26 compounds which shows a high affinity towards the Nsp15. The drug-likeness and pharmacokinetic parameters of all 26 compounds were explored, and five molecules were found to have an acceptable pharmacokinetic profile. Overall, the Glide-XP docking score and Prime-MM-GBSA binding free energy of the selected molecules were explained strong interaction potentiality towards the Nsp15 endoribonuclease. The dynamic behavior of each molecule with Nsp15 was assessed using conventional molecular dynamics (MD) simulation. The MD simulation information was strongly favors the Nsp15 and each identified ligand stability in dynamic condition. Finally, from the MD simulation trajectories, the binding free energy was estimated using the MM-PBSA method. Hence, the proposed final five molecules might be considered as potential Nsp15 modulators for SARS-CoV-2 inhibition. Image 1 • Nsp15 of SARS-CoV-2 considers as an important therapeutic target for COVID-19. • Entire Asinex antiviral database screened through multistep molecular docking. • MD simulations reveal stable interactions with putative modulators (N1–N5). • Binding free energy values suggested strong binding affinity towards Nsp15. • ADMET analyses shown accepted drug-like profile for all modulators of Nsp15. [ABSTRACT FROM AUTHOR]

• Novel cycloheptylbenzothiazole-2-carboxamide were designed. • Nine derivatives were successfully synthesised and characterised. • Good inhibitory activity found in TCP1020 bladder cancer cell lines. • Synthesized compounds have good docking score for ligand-protein complex. Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cases. The matter of concern is more severe with very limited options of treatment and lack of new drugs, cisplatin and doxorubicin are the only two drugs mostly used in therapy. This situation along with the epidemiological data calls for the development of newer better and safer agents. Herein, we report nine novel benzothiazole derivatives based on structure-based drug discovery and molecular modelling approaches. Newly designed compounds were synthesized following a four-step reaction and were characterized for structural confirmation. These novel compounds were evaluated on the MTT assay for their in vitro efficiency using the TCP1020 cell lines. These were further analysed for their mechanism of action based on in silico studies. Two compounds of the series exhibit promising results which are in agreement with the in-silico studies. It was found that the methyl group at the seventh position to the nitrogen decreases the electron affinity of the series and is thus responsible for the activity in 4e. The methyl substituted compound 4e and fluoro substituted compound 4i shows the highest activities with an IC 50 of 10.1 ± 0.2 and 7.8 ± 0.7 respectively. [ABSTRACT FROM AUTHOR]

Nipah virus (NiV) infections are highly contagious and can cause severe febrile encephalitis. An outbreak of NiV infection has reported high mortality rates in Southeast Asian countries including Bangladesh, East Timor, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, Philippines, Thailand and India. Considering the high risk for an epidemic outbreak, the World Health Organization (WHO) declared NiV as an emerging priority pathogen. However, there are no effective therapeutics or any FDA approved drugs available for the treatment of this infection. Among the known nine proteins of NiV, glycoprotein plays an important role in initiating the entry of viruses and attaching to the host cell receptors. Herein, three antiviral databases consisting of 79,892 chemical entities have been computationally screened against NiV glycoprotein (NiV-G). Particularly, multi-step molecular docking followed by extensive molecular binding interactions analyses, binding free energy estimation, in silico pharmacokinetics, synthetic accessibility and toxicity profile evaluations have been carried out for initial identification of potential NiV-G inhibitors. Further, molecular dynamics (MD) simulation has been performed to understand the dynamic properties of NiV-G protein-bound with proposed five inhibitors (G1-G5) and their interactions behavior, and any conformational changes in NiV-G protein during simulations. Moreover, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) based binding free energies (∆G) has been calculated from all MD simulation trajectories to understand the energy contribution of each proposed compound in maintaining and stabilizing the complex binding interactions with NiV-G protein. Proposed compounds showed high negative ∆G values ranging from −166.246 to −226.652 kJ/mol indicating a strong affinity towards the NiV-G protein. Unlabelled Image • Nipah Virus (NiV) is highly lethal, emerging, and count among various medically important bat-borne viruses. • A set of 79,892 compounds were screened against NiV protein through a multi-step molecular docking study. • Based on Glide_XP score, binding free energy and pharmacokinetics assessment, 5 molecules found as potential NiV protein inhibitors. • Binding interaction and molecular dynamics simulations suggested the potentiality of the selected molecules for NiV inhibition. • Binding energy calculated using MM-PBSA approach indicates strong binding affinity of the molecules towards NiV protein. [ABSTRACT FROM AUTHOR]

• Grinding as a rapid, safe, and solvent-free method for the synthesis of thiazolidinone derivatives. • New thiazolidinone derivatives target the cyclin dependent kinase 2. • From the MD simulation, the two synthesized molecules are retained inside the CDK2 receptor cavity. This work aims to synthesize thiazolidinone derivatives using a rapid, safe and solvent-free grinding assisted approach. The newly synthesized compounds have been targeted due to their bioactivity in wide pharmaceutical uses, especially, as anti-proliferative agents. Two thiazolidinone derivatives having a diverse set of crucial functional groups were diagnosed with melting point (m.p), FT-IR, 1H NMR, 13C NMR, GC-Mass and CHNS. High outputs (98% and 96%) of thiazolidinone derivatives were offered by the grinding method and the final product was produced over short reaction times (5 min). This simple strategy would potentially be promising for the preparation of thiazolidinone derivatives in abundance. Followed by synthesis both of our molecules were considered for molecular docking study against the Cyclin-Dependent Kinase 2 (CDK2) protein. A number of potential binding interactions in terms of hydrogen and hydrophobic bonds were observed with the ligand-binding amino acid of CDK2 protein. The behavior of both molecules inside the CDK2 was explored through all-atoms molecular dynamics (MD) simulations. Several parameters calculated from the MD simulation were revealed that both molecules retained inside the receptor cavity of CDK2. Hence, green synthesized both compounds were found to show strong potentiality against the CDK2 and may have significant interests in the field of pharmaceutical chemistry. [ABSTRACT FROM AUTHOR]

• Complex between BI-224436 and HIV-1 integrase was used to design novel anti-HIV inhibitors. • The de novo approach available in LigBuilder was used. • A number of criteria was used to narrow down the chemical space of initial designed 80,000 inhibitors. • Different pharmacokinetics parameters were checked for final proposed molecules. • MD simulation was performed of HIV-1 integrase complex with proposed molecules. In the present study, pharmacoinformatics paradigms include receptor-based de novo design, virtual screening through molecular docking and molecular dynamics (MD) simulation are implemented to identify novel and promising HIV-1 integrase inhibitors. The de novo drug/ligand/molecule design is a powerful and effective approach to design a large number of novel and structurally diverse compounds with the required pharmacological profiles. A crystal structure of HIV-1 integrase bound with standard inhibitor BI-224436 is used and a set of 80,000 compounds through the de novo approach in LigBuilder is designed. Initially, a number of criteria including molecular docking, in-silico toxicity and pharmacokinetics profile assessments are implied to reduce the chemical space. Finally, four de novo designed molecules are proposed as potential HIV-1 integrase inhibitors based on comparative analyses. Notably, strong binding interactions have been identified between a few newly identified catalytic amino acid residues and proposed HIV-1 integrase inhibitors. For evaluation of the dynamic stability of the protein-ligand complexes, a number of parameters are explored from the 100 ns MD simulation study. The MD simulation study suggested that proposed molecules efficiently retained their molecular interaction and structural integrity inside the HIV-1 integrase. The binding free energy is calculated through the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) approach for all complexes and it also explains their thermodynamic stability. Hence, proposed molecules through de novo design might be critical to inhibiting the HIV-1 integrase. [ABSTRACT FROM AUTHOR]

The cyclin-dependent kinase-2 (CDK2) belongs to the protein kinase family and its overexpression leads to an unusual regulation of cell-cycle which directly linked with hyperproliferation in many cancer cell types. CDK2 activation spontaneously promotes the cell cycle progression and also involved in a large number of cellular processes including cell cycle regulation, DNA replication, DNA damage response and apoptotic pathways, therefore targeting the CDK2 can be reemerged as a therapeutic boulevard to restrain cancer cell proliferation. For the last two decades, emerging evidences suggested that CDK2 inhibition draws out some antitumor/anticancer activity, which has driven the research possibility for developing next-generation newer or cost-effective inhibitors with greater specificity to CDK2. In the current work, compounds from the FooDB - a world's largest food constituents database was retrieved and curated and followed by multi-pharmacoinformatics approaches adopted to find out potential CDK2 inhibitors. The curated dataset was considered for screening through "Virtual Screening Workflow" (VSW) employed in Schrödinger suite. The numbers of cost-effective food constituents were reduced by removing low potential molecules in terms of interaction affinity and further explored for pharmacokinetics analysis. Based on strong binding interaction profiles with the lowest binding interactions affinity and energy values, four food compounds were proposed as CDK2 inhibitors. A number of key analyzing parameters from molecular dynamics (MD) simulations studies were successfully substantiated that all four proposed food compounds can act as CDK2 inhibitors based on their proficient structural and molecular interactions integrity with CDK2 protein following in the active site cavity. Furthermore, the binding free energy was calculated using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) approach from the entire trajectory frames derived in MD simulation revealed strong interaction affinity. The binding free energy was found to be in the range of −991.831 to −210.452 kJ/mol. High binding free energy was undoubtedly explained that all molecules possess strong affection towards CDK2. Hence, proposed molecules may be crucial to stop the hyperproliferation in cancer cells subjected to experimental validation. • Compounds from FooDB were virtually screened to identify potential CDK2 inhibitors. • Through virtual screening workflow four potential molecules were identified as CDK2 inhibitors. • Different pharmacokinetics parameters were checked for final proposed molecules. • 100 ns MD simulation study was performed for all proposed molecules bound with CDK2. • The binding free energy was calculated using MM-PBSA approach. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder generally developed with aging. AD slowly hammers the memory and cognitive abilities which eventually leads to abnormal behaviour, and ultimately left with disability and dependency. It is anticipated that by the year 2050, world population will experience the incidence of 100 million AD cases. It has been more than hundred years passed since AD recognized as a dreadfull disease, but there is no effective curative agent discovered against AD to date. One of the major hallmarks of the AD development is the accumulation of extracellular amyloid-beta (Aβ) plaques in the brain. In the amyloidogenic process, an extensively studied beta-secretase enzyme, known as BACE1, plays a key role in the accumulation and production of Aβ fragments. Therefore, successful inhibition of BACE1 by small molecular chemical entities can be an effective approach for anti-AD drug development. Hence, the current study has been perceived to find out potential BACE1 inhibitiors by virtual screening of entire Asinex chemical library database through multi-step molecular docking methodologies. Further, sequential screening of in-silico pharmacokinetics, molecular dynamic (MD) simulations analyses along with binding free energy estimation were performed. Comparative analyses and characteristics of molecular binding interactions assessment finally suggests that five molecules (B1–B5) to be the most promising BACE1 inhibitors. Molecular interactions analyses revealed that either one or both the catalytic dyad residues (Asp32 and Asp228) of BACE1 has formed strong molecular interactions with all the proposed molecules. Not only the catalytic dyad residues are involved in the formation of molecular binding interactions but also other important non-Asp binders residues such as Gly34, Tyr71, Trp115, Arg128, Lys224, Gly230, Thr231, Thr232, Arg235, Thr329, and Val332 found to interact with the selected compounds. Moreover, the dynamic behaviour of proposed molecules and BACE1 was explored through all-atoms MD simulation study for 100 ns time span. Analysis of MD simulation trajectories explained that all identified molecules are efficient enough to retain the structural and molecular interactions integrity inside the receptor cavity of BACE1 in dynamic environment. Finally, the binding free energy of each molecule has calculated from MD simulation trajectories through MM-PBSA method and found that all molecules possess a strong binding affinity towards the BACE1. The high negative binding free energies are found to be within the range of −994.978 to −561.562 kJ/mol for the identified compounds. Henceforth, analyses of extensively studied multi-cheminformatics approaches explained that proposed molecules might be promising BACE1 inhibitors for therapeutic application in AD, subjected to experimental validation. Image 1 • CNS-Asinex database was virtually screened to identify potential BACE1 inhibitors. • Through docking and VSW five potential molecules were identified as BACE1 inhibitors. • Different pharmacokinetics parameters were checked for final proposed molecules. • MD simulation was performed of BACE1 complex with proposed molecules. • The binding energy was calculated using MM-PBSA approach. [ABSTRACT FROM AUTHOR]

• Wild type Catalase-peroxidase enzyme (WT katG) mutated into five mutant katG (MT katG). • Molecular docking was performed WT and MT katG. • Screening was performed based on binding energy of Isoniazid and promising katG inhibitors proposed. • MD simulation was performed for MT katG-proposed molecules complex. • Binding energy of proposed molecules was calculated using MM-PBSA approach. Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the present age, due to the rapid increase in antibiotic resistance worldwide, TB has become a major threat to human life. Regardless of significant efforts have been inclined to improve the healthcare systems for improving diagnosis, treatment, and anticipatory measures controlling TB is challenging. To date, there are no such therapeutic chemical agents available to fight or control the bacterial drug-resistance. The catalase-peroxidase enzyme (katG) which encoded by the katG gene of Mtb is most frequently getting mutated and hence promotes Isoniazid resistance by diminishing the normal activity of katG enzyme. In the current study, an effort has been intended to find novel and therapeutically active antibacterial chemical compounds through pharmacoinformatics methodologies. Initially, the five mutant katG were generated by making mutation of Ser315 by Thr, Ile, Arg, Asn, and Gly followed by structural optimizations. About eight thousand small molecules were collected from the Asinex antibacterial library. All molecules were docked to active site of five mutant katG and wild type katG. To narrow down the chemical space several criteria were imposed including, screening for highest binding affinity towards katG proteins, compounds satisfying various criterion of drug-likeliness properties like Lipinski's rule of five (RO5), Veber's rule, absorption, distribution, metabolism, and excretion (ADME) profile, and synthetic accessibility. Finally, five molecules were found to be important antibacterial katG inhibitors. All the analyzed parameters suggested that selected molecules are promising in nature. Binding interactions analysis revealed that proposed molecules are efficient enough to form a number of strong binding interactions with katG proteins. Dynamic behavior of the proposed molecules with katG protein was evaluated through 100 ns molecular dynamics (MD) simulation study. Parameters calculated from the MD simulation trajectories adjudged that all molecules can form stable complexes with katG. High binding free energy of all proposed molecules definitely suggested strong affection towards the katG. Hence, it can be concluded that proposed molecules might be used as antibacterial chemical component subjected to experimental validation. [ABSTRACT FROM AUTHOR]