Enhancement of cellulase production by cellulolytic bacteria SB125 in submerged fermentation medium and biochemical characterization of the enzyme.

Microbial diversity from indigenous cultures has the potential to accelerate lignocellulose degradation through enzymes and make composting economically feasible. Therefore, this study is designed to boost cellulase output from a bacterial strain obtained from soil using a one-variable-at-a-time approach and response surface methodology. The bacteria recognized as Bacillus tequilensis (ON754229) produced the maximum cellulase at a temperature of 37 °C, pH -7.0, and incubation time of 72 h. A major contribution was anticipated by glucose (17 %) and ammonium sulfate (11 %) with cellulase activity of 0.56 U/mL in the optimized medium. The enzyme possessed activity of CMCase, FPase, and amylase of 0.589 µmol/min, 1.22 µmol/min, and 0.92 µmol/min respectively. SDS-PAGE showed a 65 kDa molecular weight of the enzyme capable of degrading cellulose, as confirmed by zymogram analysis. The enzyme showed relatively moderate thermo-stability towards neutral pH conditions possessing optimum conditions at pH 6.5 and temperature of 50 °C. The Km and Vmax values were 11.44 mM and 0.643 µmol/min respectively. The presence of MgSO4, ZnSO4, and Triton X- 100 increased the enzymatic reaction however AgNO3, EDTA, and HgCl2 altered the activation process. These results showed cellulase from B. tequilensis SB125 would be suitable for conventional industrial processes that convert biomass into biofuels.

Exploring the interaction of tepotinib with calf thymus DNA using molecular dynamics simulation and multispectroscopic techniques.

In recent times, there has been a surge in the discovery of drugs that directly interact with DNA, influencing gene expression. As a result, understanding how biomolecules interact with DNA has become a major area of research. One such drug is Tepotinib (TPT), an FDA-approved anti-cancer medication known as a MET tyrosine kinase inhibitor, used in chemotherapy for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations. In our study, we adopted both biophysical and in-silico methods to investigate the binding relationship of TPT and ctDNA. The absorption spectra of ctDNA exhibited a hypochromic effect when titrated with TPT and the binding constant of TPT-ctDNA complex was calculated, Ka = 9.91 × 104 M-1. By computing bimolecular enhancement constant (KB) and thermodynamic enhancement constant (KD) in fluorometric investigations, it was found that the fluorescence enhancement is a result of a static process involving the ctDNA-TPT complex formation in the ground state, as opposed to a dynamic process. The displacement assay results further supported this finding, showing that TPT exhibits a binding preference for minor groove of ct-DNA and was also demonstrated by KI quenching and CD spectroscopy. The molecular docking and molecular dynamic simulations validated TPT's groove binding nature and binding pattern with ctDNA, respectively. Thus, the results of our present investigation offer valuable insights into the interaction between TPT and ctDNA. It is evident that TPT, as an anti-cancer medication, binds to the minor groove of ctDNA.

Exploring quantum computational, molecular docking, and molecular dynamics simulation with MMGBSA studies of ethyl-2-amino-4-methyl thiophene-3-carboxylate.

2-aminothiophenes derivative, Ethyl-2-amino-4-methyl thiophene-3-carboxylate (EAMC) has been synthesized, characterized, and investigated quantum chemically. It was experimentally investigated by different spectroscopic methods like- NMR (1H-NMR and 13C-NMR), FT-IR, and UV-Visible. B3LYP method and 6-311++G(d,p) basis set were employed for optimization of molecular structure and calculation of wave numbers of normal modes of vibrations and various other important parameters. Calculated bond lengths and angles were compared with the experimental bond lengths and Bond Angle Parameters. Optimized bond parameters and experimental bond parameters were found in good agreement. Complete potential energy distribution assignments were done successfully by VEDA. The HOMO/LUMO energy gap emphasizes adequate charge transfer happening within the molecule. A study of donor-acceptor interconnections was done via NBO analysis. MEP surface analysis was done to demonstrate charge distribution and reactive areas qualitatively in the molecule. The degree of relative localization of electrons was analyzed via ELF Diagram. The Fukui function analysis showed possible sites for attacks by different substituents. By using the TD-DFT method and PCM solvent model, the UV-Vis spectrum (gas, methanol, DMSO) and the maximum absorption wavelength was computed and compared with experimental data. 3D and 2D intermolecular interactions in the crystal were analyzed via Hirshfeld surface analysis and fingerprint plots reveal that the EAMC crystal was stabilized by H--H/H--H/C--H bond formation. The molecular docking was done with 7 different protein receptors on the molecule to find the best ligand-protein interactions. Molecular dynamic simulations and MMGBSA calculations were also carried out to find out the best binding of the ligand with the protein.Communicated by Ramaswamy H. Sarma.

Whole-Blood Metabolomics of a Rat Model of Repetitive Concussion.

Mild traumatic brain injury (mTBI) and repetitive mTBI (RmTBI) are silent epidemics, and so far, there is no objective diagnosis. The severity of the injury is solely based on the Glasgow Coma Score (GCS) scale. Most patients suffer from one or more behavioral abnormalities, such as headache, amnesia, cognitive decline, disturbed sleep pattern, anxiety, depression, and vision abnormalities. Additionally, most neuroimaging modalities are insensitive to capture structural and functional alterations in the brain, leading to inefficient patient management. Metabolomics is one of the established omics technologies to identify metabolic alterations, mostly in biofluids. NMR-based metabolomics provides quantitative metabolic information with non-destructive and minimal sample preparation. We employed whole-blood NMR analysis to identify metabolic markers using a high-field NMR spectrometer (800 MHz). Our approach involves chemical-free sample pretreatment and minimal sample preparation to obtain a robust whole-blood metabolic profile from a rat model of concussion. A single head injury was given to the mTBI group, and three head injuries to the RmTBI group. We found significant alterations in blood metabolites in both mTBI and RmTBI groups compared with the control, such as alanine, branched amino acid (BAA), adenosine diphosphate/adenosine try phosphate (ADP/ATP), creatine, glucose, pyruvate, and glycerphosphocholine (GPC). Choline was significantly altered only in the mTBI group and formate in the RmTBI group compared with the control. These metabolites corroborate previous findings in clinical and preclinical cohorts. Comprehensive whole-blood metabolomics can provide a robust metabolic marker for more accurate diagnosis and treatment intervention for a disease population.

Preparation of a Pt(II)-3-Hydroxy-2-tolyl-4H-chromen-4-one Complex Having Antimicrobial, Anticancerous, and Radical Scavenging Activities with Related Computational Studies.

A novel benzopyran-based platinum (II)-3-hydroxy-2-tolyl-4H-chromen-4-one (HToC) complex has been prepared and studied by UV-visible spectrophotometry. The study is based on the colored complexation between Pt(II) and HToC in the pH range of 8.92-9.21, resulting in the formation of a stable binary yellow complex exhibiting λmax at 509-525 nm. The formed complex maintains linearity between 0.0 and 1.8 µg Pt(II) mL-1. The well-known qualitative analytical methods, including Job's method of continuous variations and the mole ratio approach, have both proven that the stoichiometry of the complex is 1:2 [Pt(II)/HToC]. Hence, the analytical results suggest that the formed platinum complex exhibits a square planar geometry. The values of various attributes corresponding to spectrophotometric studies and statistical calculations, such as the molar extinction coefficient (6.790 × 104 L mol-1 cm-1), Sandell's sensitivity (0.0029 µg Pt(II) cm-2), standard deviation (± 0.0011), RSD (0.317%), limit of detection (0.0147 µg mL-1) and correlation coefficient (0.9999), show that the performed study satisfies all of the criteria for good sensitivity, versatility, and cost-effectiveness. In order to have an apprehension of the molecular geometry and other structural specifics of the complex, DFT studies have been carried out. The in vitro anticancer potential of the ligand and its platinum complex in the human breast cancer cell line (T-27D), as determined by the MTT assay, reveals that the complex has better antiproliferative potential than the ligand. The antimicrobial potential of the complex has been successfully tested against both Gram-positive and -negative bacteria. Antioxidant capacity results suggest the better radical scavenging capacity of the complex than that of the ligand.

A 3D copper (II) coordination polymer based on sulfanilic acid ligand (CP 1) for efficient biomolecular interaction with bovine serum albumin: spectroscopic, molecular modelling and DFT analysis.

Several biochemical reactions occur during the interaction of metal complexes and proteins due to conformational modifications in the structure of the protein, which provide fundamental knowledge of the effect, mechanism, and transport of many drugs throughout the body. Here, we report the synthesis, identification, and impact of the 3-dimensional Copper(II)sulfanilic acid coordination polymer (CP 1) on interactions with bovine serum albumin (BSA). The CP 1 was synthesized via a simple hot stirring method, and the single crystal XRD confirms the effective bonding interactions between metal and organic ligand, forming a crystalline polymeric chain and the topological study shows the sql type of underlying net topology. Powder XRD, Fourier transform infrared spectroscopy, and thermogravimetric analysis were also performed. Moreover, DFT/B3LYP calculations provide chemical precision for the resulting complex. Further, the changes that occur in the secondary structure of protein when CP 1 binds with BSA as well as its binding capacity were investigated via circular dichroism analysis and spectroscopic methods such as UV-absorption spectroscopy and fluorescence spectroscopy, respectively. The CP 1/BSA complex melting point was also measured, and its temperature-dependent heat denaturation was studied along with molecular docking.Communicated by Ramaswamy H. Sarma.

Experimental and theoretical magnetostructural studies on discrete heterometallic cyanide-bridged dinuclear FeIIIMnII and tetranuclear FeIII2CuII2 complexes bearing tripodal pyrazolyl borate and tetradentate phenolate-based ligands.

Two new complexes [FeIII(Tp)(CN)2(µ-CN)MnIICl(HL1)]·3DMF (1) and {[FeIII(Tp)(CN)(µ2-NC)2CuII(HL2)](ClO4)}2·6DMF (2) (HL1 = 2-((((1-methylbenzimidazol-2-yl)methyl)(pyridin-2-ylmethyl)amino)methyl)phenol and HL2 = 2-(((pyridin-2-ylmethyl)(quinolin-2-ylmethyl)-amino)methyl)phenol) have been synthesized and characterized by elemental analysis and IR and UV/vis spectroscopy. Structural analysis revealed that 1 is a discrete dinuclear coordination complex and 2 is a discrete tetranuclear coordination complex. In complex 1, each MnII is in a distorted octahedral MN4OCl environment where coordination is satisfied by three nitrogen atoms and one oxygen atom of the ligand, and a chloride group and one nitrogen atom from cyanide. In complex 2, each Cu is in a distorted octahedral MN5O environment where coordination is satisfied by three nitrogen atoms and one oxygen atom of the ligand, and two nitrogen atoms from two cyanides. Direct current (dc) variable-temperature magnetic susceptibility measurements on polycrystalline samples of 1 and 2 were carried out in the temperature range of 1.8-300 K. Investigation of the magnetic properties reveals the occurrence of weak antiferromagnetic coupling between the low-spin FeIII (S = 1/2) ions and high-spin MnII (S = 5/2) ions in 1, while 2 exhibits ferro- and antiferromagnetic coupling between the metal ions in the tetranuclear CuII2FeIII2 unit. DFT calculations show ferromagnetic coupling in both complexes, although this appears to be weak in the case of complex 1. In addition, magnetostructural correlations reveal the magnetic behavior against Mn-N-C and Fe-C-N angles in 1 and Cu-N-C and Fe-C-N angles in 2.

Flubendiamide induced genetic and cellular damages directly influence the life cycle of the oriental leaf worm, Spodoptera litura.

Indiscriminate uses of insecticide greatly damage the environment as well as non-target organisms. Thus, multiple levels of bioassays can help better management of our environment. Flubendiamide is a phthalic acid diamide insecticide that ceases the function of insect muscle leading to paralysis and death. Here, we aimed to explore the effects of Flubendiamide on the life cycle of Spodoptera litura vis-a-vis the mode of action. Fourth instar larvae of the same age (120 ± 2 h) and size were fed with different concentrations (20-80 µg/mL) of Flubendiamide for 12-72 h. We performed a pharmacokinetics study, different biochemical assays, p450, Ecdysone receptor (EcR) and other genes expression analyses by Real-Time PCR and gross damages by Dye exclusion assay and histopathology. Our results demonstrate that the mean concentration of Flubendiamide after 48 h is 9.907 µg/mL and (i) altered the molting, metamorphosis, and reproduction at 80 µg/mL (24 h) (ii) increases all oxidative stress parameters (ROS/RNS, MDA, 8OHdG), decreases oxidative defense mechanisms (SOD, CAT, GST) at 80 µg/mL (48 h) and p450 in a time and concentration-dependent manner, (iii) activates CncC/Maf apoptotic pathways at 80 µg/mL concentration at 24 h while the expression declined from 48 h onwards, (iii) downregulates the EcR expression in a time and concentration-dependent manner, which might be responsible for disturbed molting, metamorphosis, and reproduction, and (iv) increase the expression of apoptotic genes (Caspase 1, -3, and - 5), in time and concentration-dependent manner causing gross morphological and histological damages. In conclusion, indiscriminate use of this insecticide can affect the ecosystem and have the capacity to cause multiple hazardous effects on experimental organisms. Thus, it warrants further investigations to improve and optimize the integrated pest management packages, including Flubendiamide for better management.

Glycation reduces the binding dynamics of aflatoxin B1 to human serum albumin: a comprehensive spectroscopic and computational investigation.

Aflatoxin B1 (AFB1), a potent mutagen, is synthesized by Aspergillus parasiticus and Aspergillus flavus. Human serum albumin (HSA) is a globular protein with diverse roles. As AFB1 is ingested with food and is transported in the body via blood, it becomes pertinent to comprehend the effect of the binding of this toxin on the structure and conformation of HSA, which may help to get insight into the toxic effect of the exposure of the mycotoxin. In this study, multi-spectroscopic approaches have been used to evaluate the binding efficiency of AFB1 with both the native HSA (nHSA) and the glycated HSA (gHSA). Steady-state fluorescence spectroscopy reveals the static type of fluorescence quenching in the fluorescence emission spectra of nHSA and gHSA in the presence of AFB1. The binding constant (Kb) is calculated to be 6.88 × 104 M-1 for nHSA, while a reduced Kb value of 2.95 × 104 M-1 has been obtained for gHSA. The circular dichroism study confirms the change in the secondary structure of nHSA and gHSA in the presence of AFB1, followed by alterations in the melting temperature (Tm) of nHSA and gHSA. In silico computational findings envisaged the amino acid residues and bonds involved in the binding of nHSA and gHSA with AFB1. The comprehensive study analyzes the binding effectiveness of AFB1 with nHSA and gHSA and shows reduced binding of AFB1 to gHSA.Communicated by Ramaswamy H. Sarma.

As revealed by UV-absorption spectroscopy, the hyperchromic effect was more prominent in nHSA than gHSA in the presence of AFB₁.The binding constant (K_b) obtained for the nHSA-AFB₁ complex was 6.88 × 10⁴ M^−1, and the gHSA-AFB₁ complex yielded K_b value of 2.95 × 10⁴ M⁻¹.Negative enthalpy change (ΔH) and entropy change (ΔS) suggested hydrogen bonding and van der Waals interaction as stabilizing forces of nHSA-AFB₁ and gHSA-AFB₁ complex.Site markers displacement assay suggested Sudlow's site I as the binding site for AFB₁ in nHSA and gHSA.Circular dichroism study showed that AFB₁ induced secondary structural changes in nHSA and gHSA.Melting temperature (T_m) increased in nHSA and decreased in gHSA in the presence of AFB₁.Molecular docking results confirmed Lys-195, Arg-222 and Arg-257 as hydrogen bonding residues in the nHSA-AFB₁ complex and Arg-222 and Lys-199 residues were involved in hydrogen bonding in the gHSA-AFB₁ complex.

Elucidation of binding dynamics of tyrosine kinase inhibitor tepotinib, to human serum albumin, using spectroscopic and computational approach.

Tepotinib (TPT), an anticancer drug, is a fibroblast growth factor receptor inhibitor approved by the FDA for the chemotherapy of urothelial carcinoma. The binding of anticancer medicines to HSA can affect their pharmacokinetics and pharmacodynamics. The absorption, fluorescence emission, circular dichroism, molecular docking, and simulation studies were used to evaluate the binding relationship between TPT and HSA. The absorption spectra exhibited a hyperchromic effect upon the interaction of TPT with HSA. The Stern-Volmer and binding constant of the HSA-TPT complex demonstrates that fluorescence quenching is triggered by a static rather than a dynamic process. Further, the displacement assays and molecular docking results revealed that TPT preferred binding to site III of HSA. Circular dichroism spectroscopy confirmed that TPT binding to HSA induces conformational changes and reduces α-helical content. The thermal CD spectra reveal that tepotinib enhances protein's stability in the temperature range of 20 to 90 °C. The findings of MDS studies provide further evidence for the stability of the HSA-TPT complex. Consequently, the findings of the present investigation provide a clear picture of the impacts of TPT on HSA interaction. These interactions are thought to make the microenvironment around HSA more hydrophobic than in its native state.

Studies towards investigation of Naphthoquinone-based scaffold with crystal structure as lead for SARS-CoV-19 management.

In this work, 1-(4-bromophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-3,8­dione (1-(4-BP)DHCBN-3,8-D) has been characterized by single crystal X-ray to get it's crystal structure with R(all data) - R1 = 0.0569, wR2 = 0.0824, 13C and 1HNMR, as well as UV-Vis and IR spectroscopy. Quantum chemical calculations via DFT were used to predict the compound structural, electronic, and vibrational properties. The molecular geometry of 1-(4-BP)DHCBN-3,8-Dwas optimized utilizing the B3LYP functional at the 6-311++G(d,p) level of theory. The Infrared spectrum has been recorded in the range of 4000-550 cm-1. The Potential Energy Distribution (PED) assignments of the vibrational modes were used to determine the geometrical dimensions, energies, and wavenumbers, and to assign basic vibrations. The UV-Vis spectra of the titled compound were recorded in the range of 200-800 nm in ACN and DMSO solvents. Additionally, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap and electronic transitions were determined using TD-DFT calculations, which also simulate the UV-Vis absorption spectrum. Natural Bond Orbital (NBO) analysis can be used to investigate electronic interactions and transfer reactions between donor and acceptor molecules. Temperature-dependent thermodynamic properties were also calculated. To identify the interactions in the crystal structure, Hirshfeld Surface Analysis was also assessed. The Molecular Electrostatic Potential (MEP) and Fukui functions were used to determine the nucleophilic and electrophilic sites. Additionally, the biological activities of 1-(4-BP)DHCBN-3,8-D were done using molecular docking. These results demonstrate a significant therapeutic potential for 1-(4-BP)DHCBN-3,8-D in the management of Covid-19 disorders. Molecular Dynamics Simulation was used to look at the stability of biomolecules.

Quantum Computational, Spectroscopic (FT-IR, FT-Raman, NMR, and UV-Vis) Hirshfeld Surface and Molecular Docking-Dynamics Studies on 5-Hydroxymethyluracil (Monomer and Trimer).

For many decades, uracil has been an antineoplastic agent used in combination with tegafur to treat various human cancers, including breast, prostate, and liver cancer. Therefore, it is necessary to explore the molecular features of uracil and its derivatives. Herein, the molecule's 5-hydroxymethyluracil has been thoroughly characterized by NMR, UV-Vis, and FT-IR spectroscopy by means of experimental and theoretical analysis. Density functional theory (DFT) using the B3LYP method at 6-311++G(d,p) was computed to achieve the optimized geometric parameters of the molecule in the ground state. For further investigation and computation of the NLO, NBO, NHO analysis, and FMO, the improved geometrical parameters were utilized. The potential energy distribution was used to allocate the vibrational frequencies using the VEDA 4 program. The NBO study determined the relationship between the donor and acceptor. The molecule's charge distribution and reactive regions were highlighted using the MEP and Fukui functions. Maps of the hole and electron density distribution in the excited state were generated using the TD-DFT method and PCM solvent model in order to reveal electronic characteristics. The energies and diagrams for the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) were also provided. The HOMO-LUMO band gap estimated the charge transport within the molecule. When examining the intermolecular interactions in 5-HMU, Hirshfeld surface analysis was used, and fingerprint plots were also produced. The molecular docking investigation involved docking 5-HMU with six different protein receptors. Molecular dynamic simulation has given a better idea of the binding of the ligand with protein.

Molecular interactions of esculin with bovine serum albumin and recognition of binding sites with spectroscopy and molecular docking.

Esculin is structurally a hydroxycoumarin found in various medicinal plants. This study investigates the binding mode of esculin with bovine serum albumin by employing numerous spectroscopic studies and molecular docking approaches. Ultraviolet absorption spectroscopy revealed ground state complex formation between esculin and bovine serum albumin. At the same time, steady-state fluorescence studies showed quenching in the fluorescence emission spectra of BSA in the presence of esculin. To get insight into the location of the binding pocket of esculin on BSA, warfarin and ibuprofen site markers were used. Competitive site marker displacement assay revealed that esculin binds to Sudlow's site I (subdomain IIA) in bovine serum albumin. Thermodynamic parameters suggested that hydrogen bonding and van der Waals interaction stabilizes the esculin-BSA complex. Förster's non-radiation energy transfer analysis described the high propensity of energy transfer between bovine serum albumin and esculin. The molecular docking approach facilitated locating the binding pocket, amino acid residues involved, types of interacting forces, and binding energy (ΔG) between esculin and BSA. Circular dichroism revealed the effect of the binding of esculin on the secondary structure and helped understand the thermal unfolding profile of BSA in the presence of esculin.Communicated by Ramaswamy H. Sarm.

Evaluation of experimental, computational, molecular docking and dynamic simulation of flucytosine.

Flucytosine (5-fluorocytosine), a fluorine derivative of pyrimidine, has been studied both experimentally and quantum chemically. To obtain the optimized structure, vibrational frequencies and other various parameters, the B3LYP method with a 6-311++G(d,p) basis set was used. Atom-in-molecule theory was used to calculate the binding energies, ellipticity and isosurface projection by electron localization of the molecule (AIM). In addition, the computational results from IR and Raman were compared with the experimental spectra. NBO analysis was used to analyze the donor and acceptor interactions. To know the reactive region of the molecule, the molecular electrostatic potential (MEP) and Fukui functions were determined. The UV-Vis spectrum calculated by the TD-DFT/PCM method was also compared with the experimentally determined spectrum. The HOMO-LUMO energy outcomes proved that there was a good charge exchange occurring within the molecule. With DMSO and MeOH as the solvents, maps of the hole and electron density distribution (EDD and HDD) were produced in an excited state. An electrophilicity index parameter was looked at to theoretically test the bioactivity of the compound. To find the best ligand-protein interactions, molecular docking was also carried out with various receptor proteins. In order to verify the inhibitory potency for the receptor protein complex predicted by docking and molecular dynamic simulation studies, the binding free energy of the receptor protein complex was calculated. Using the MM/GBSA technique, we determined the docked complex's binding free energy. To confirm the molecule's drug similarity, a biological drug similarity investigation was also executed.Communicated by Ramaswamy H. Sarma.

Oxadiazole Schiff Base as Fe3+ Ion Chemosensor: "Turn-off" Fluorescent, Biological and Computational Studies.

Compound, (E)-5-(4-((thiophen-2-ylmethylene)amino)phenyl)-1,3,4-oxadiazole-2-thiol (3) was synthesized via condensation reaction of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol with thiophene-2-carbaldehyde in ethanol. For the synthesis and structural confirmation the FT-IR, 1H, 13C-NMR, UV-visible spectroscopy, and mass spectrometry were carried out. The long-term stability of the probe (3) was validated by the experimental as well as theoretical studies. The sensing behaviour of the compound 3 was monitored with various metal ions (Ca2+, Cr3+, Fe3+, Co2+, Mg2+, Na+, Ni2+, K+) using UV- Vis. and fluorescence spectroscopy techniques by various methods (effect of pH and density functional theory) which showing the most potent sensing behaviour with iron. Job's plot analysis confirmed the binding stoichiometry ratio 1:1 of Fe3+ ion and compound 3. The limit of detection (LOD), the limit of quantification (LOQ), and association constant (Ka) were calculated as 0.113 µM, 0.375 µM, and 5.226 × 105 respectively. The sensing behavior was further confirmed through spectroscopic techniques (FT-IR and 1H-NMR) and DFT calculations. The intercalative mode of binding of oxadiazole derivative 3 with Ct-DNA was supported through UV-Vis spectroscopy, fluorescence spectroscopy, viscosity, cyclic voltammetry, and circular dichroism measurements. The binding constant, Gibb's free energy, and stern-volmer constant were find out as 1.24 × 105, -29.057 kJ/mol, and 1.82 × 105 respectively. The cleavage activity of pBR322 plasmid DNA was also observed at 3 × 10-5 M concentration of compound 3. The computational binding score through molecular docking study was obtained as -7.4 kcal/mol. Additionally, the antifungal activity for compound 3 was also screened using broth dilution and disc diffusion method against C. albicans strain. The synthesized compound 3 showed good potential scavenging antioxidant activity against DPPH and H2O2 free radicals.

Crystal Structure, Topology, DFT and Hirshfeld Surface Analysis of a Novel Charge Transfer Complex (L3) of Anthraquinone and 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic Acid (L2) Exhibiting Photocatalytic Properties: An Experimental and Theoretical Approach.

Here, we report a facile route to the synthesizing of a new donor-acceptor complex, L3, using 4-{[(anthracen-9-yl)meth-yl] amino}-benzoic acid, L2, as donor moiety with anthraquinone as an acceptor moiety. The formation of donor-acceptor complex L3 was facilitated via H-bonding and characterized by single-crystal X-ray diffraction. The X-ray diffraction results confirmed the synthesized donor-acceptor complex L3 crystal belongs to the triclinic system possessing the P-1 space group. The complex L3 was also characterized by other spectral techniques, viz., FTIR and UV absorption spectroscopy, which confirmed the formation of new bonds between donor L2 moiety and acceptor anthraquinone molecule. The crystallinity and thermal stability of the newly synthesized complex L3 was confirmed by powdered XRD and TGA analysis and theoretical studies; Hirshfeld surface analysis was performed to define the type of interactions occurring in the complex L3. Interestingly, theoretical results were successfully corroborated with experimental results of FTIR and UV absorption. The density functional theory (DFT) calculations were employed for HOMO to LUMO; the energy gap (∆E) was calculated to be 3.6463 eV. The complex L3 was employed as a photocatalyst for the degradation of MB dye and was found to be quite efficient. The results showed MB dye degraded about 90% in 200 min and followed the pseudo-first-order kinetic with rate constant k = 0.0111 min-1 and R2 = 0.9596. Additionally, molecular docking reveals that the lowest binding energy was -10.8 Kcal/mol which indicates that the L3 complex may be further studied for its biological applications.

Investigating binding dynamics of trans resveratrol to HSA for an efficient displacement of aflatoxin B1 using spectroscopy and molecular simulation.

Resveratrol is a polyphenol belonging to the class stilbenes. The active and stable form of resveratrol is trans-resveratrol. This polyphenol is bestowed with numerous biological properties. Aflatoxin B1 is a hepato-carcinogen and mutagen that is produced by Aspergillus species. In this study, the interaction of trans-resveratrol with HSA followed by competitive dislodging of AFB1 from HSA by trans-resveratrol has been investigated using spectroscopic studies. The UV-absorption studies revealed ground state complex formation between HSA and trans-resveratrol. Trans-resveratrol binds strongly to HSA with the binding constant of ~ 107 M-1 to a single binding site (n = 1.58), at 298.15 K. The Stern-Volmer quenching constant was calculated as 7.83 × 104 M-1 at 298.15 K, suggesting strong fluorescence quenching ability of trans-resveratrol. Site markers displacement assay projected subdomain IIA as the binding site of trans-resveratrol to HSA. The molecular docking approach envisages the amino acid residues involved in the formation of the binding pocket. As confirmed from the site marker displacement assays, both trans-resveratrol and AFB1 binds to HSA in the same binding site, subdomain IIA. The study explores the ability of trans-resveratrol to displace AFB1 from the HSA-AFB1 complex, thereby affecting the toxicokinetic behavior of AFB1 associated with AFB1 exposure.

A Review on the Therapeutic Role of TKIs in Case of CML in Combination With Epigenetic Drugs.

Chronic myeloid leukemia is a malignancy of bone marrow that affects white blood cells. There is strong evidence that disease progression, treatment responses, and overall clinical outcomes of CML patients are influenced by the accumulation of other genetic and epigenetic abnormalities, rather than only the BCR/ABL1 oncoprotein. Both genetic and epigenetic factors influence the efficacy of CML treatment strategies. Targeted medicines known as tyrosine-kinase inhibitors have dramatically improved long-term survival rates in CML patients during the previous 2 decades. When compared to earlier chemotherapy treatments, these drugs have revolutionized CML treatment and allowed most people to live longer lives. Although epigenetic inhibitors' activity is disrupted in many cancers, including CML, but when combined with TKI, they may offer potential therapeutic strategies for the treatment of CML cells. The epigenetics of tyrosine kinase inhibitors and resistance to them is being studied, with a particular focus on imatinib, which is used to treat CML. In addition, the use of epigenetic drugs in conjunction with TKIs has been discussed. Resistance to TKIs is still a problem in curing the disease, necessitating the development of new therapies. This study focused on epigenetic pathways involved in CML pathogenesis and tumor cell resistance to TKIs, both of which contribute to leukemic clone breakout and proliferation.

Crystal structure, Hirshfeld and electronic transition analysis of 2-[(1H-benzimidazol-1-yl)meth-yl]benzoic acid.

In the title compound, C15H12N2O2, the benzimidazole ring system is inclined to the benzene ring by 78.04 (10)°. The crystal structure features O-H⋯N and C-H⋯O hydrogen bonding and C-H⋯π and π-π inter-actions, which were investigated using Hirshfeld surface analysis.

Aflatoxin B1 Induced Structural and Conformational Changes in Bovine Serum Albumin: A Multispectroscopic and Circular Dichroism-Based Study.

Aflatoxin B1 (AFB1) is a mutagen that has been categorized as a group 1 human carcinogen by the International Agency for Research on Cancer. It is produced as a secondary metabolite by soil fungi Aspergillus flavus and Aspergillus parasiticus . Here, in this study, the effect of AFB1 on the structure and conformation of bovine serum albumin (BSA) using multispectroscopic tools like fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, and circular dichroism spectropolarimetry has been ascertained. Ultraviolet absorption spectroscopy revealed hyperchromicity in the absorption spectra of BSA in the presence of AFB1. The binding constant was calculated in the range of 104 M-1, by fluorescence spectroscopy suggesting moderate binding of the toxin to BSA. The study also confirms the static nature of fluorescence quenching. The stoichiometry of binding sites was found to be unity. The competing capability of warfarin for AFB1 was higher than ibuprofen as calculated from site marker displacement assay. Förster resonance energy transfer confirmed the high efficiency of energy transfer from BSA to AFB1. Circular dichroism spectropolarimetry showed a decrease in the α-helix in BSA in the presence of AFB1. The melting temperature of BSA underwent an increment in the presence of a mycotoxin from 62.5 to 70.3 °C. Molecular docking confirmed the binding of AFB1 to subdomain IIA in BSA.