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.

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.

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.

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.

Prevalence of diabetes and prediabetes in district Swat Pakistan.

OBJECTIVE: To determine the prevalence of pre-diabetes and diabetes and its associated risk factors in adult population. METHODS: The cross-sectional population-based study was conducted from January to March 2018 in urban and rural areas of Swat, Pakistan, and comprised subjects aged 20-89 years. After a minimum 10-hour overnight fast, blood glucose was tested for pre-diabetes and diabetes according to the World Health Organization recommendations. Data was analysed using SPSS 21. RESULTS: Of the 1447 subjects, 837 (58%) were females and 610 (42%) males. The largest age group was 20-29 years with 322 (22.3) subjects. Pre-diabetes was found in 309 (21.4%) subjects and diabetes in 138 (9.52%). Higher age, urbanisation, family history of diabetes, weight, exercise, hypertension, monthly income and education were found to be significant risk factors for pre-diabetes and diabetes (p<0.05). CONCLUSIONS: Every 10th resident of Swat was found to have diabetes, and every one in five had pre-diabetes.

Gonadotropin and tumorigenesis: Direct and indirect effects on inflammatory and immunosuppressive mediators and invasion.

Human chorionic gonadotropin (hCG), a hormone essential for pregnancy, is also ectopically expressed by a variety of cancers and is associated with poor prognosis; molecular mechanisms which may contribute to tumor progression remain ill-defined. Exogenous hCG enhanced the viability of human colorectal and lung cancer cells and promoted the growth of syngeneic tumors in mice. It induced the synthesis of VEGF, IL-8, matrix metalloprotease (MMP)-2 and MMP-9, and increased invasiveness in an MMP-dependent manner. While inducing the secretion of the tumor-associated extra-cellular matrix proteoglycan versican from tumor cells, hCG consequently caused the TLR-2-mediated generation of the inflammatory, tumor-associated cytokines TNF-α and IL-6 from peripheral blood adherent cells. The molecule up-modulated the Treg-associated transcription factor FOXP3 in tumor cells and increased the secretion of TGFß and IL-10, thereby inhibiting T cell proliferation and inducing the differentiation FOXP3- CD4+ CD25- cells into functional FOXP3+ CD4+ CD25+ suppressor cells. Co-culture of hCG-treated tumor cells with mature bone-marrow derived dendritic cells induced the generation of active indoleamine deoxygenase. While anti-hCG antibodies restricted the growth of implanted tumor cells in nude mice, immunization of immune competent mice with a ßhCG-TT conjugate supplemented with Mycobacterium indicus pranii provided synergistic survival benefit in animals implanted with syngeneic, hCG-responsive tumor cells. These studies elucidate the pathways by which hCG can promote tumorigenesis, providing further rationale for anti-hCG vaccination in the treatment of gonadotropin-sensitive tumors. © 2016 Wiley Periodicals, Inc.

DYZ1 arrays show sequence variation between the monozygotic males.

BACKGROUND: Monozygotic twins (MZT) are an important resource for genetical studies in the context of normal and diseased genomes. In the present study we used DYZ1, a satellite fraction present in the form of tandem arrays on the long arm of the human Y chromosome, as a tool to uncover sequence variations between the monozygotic males. RESULTS: We detected copy number variation, frequent insertions and deletions within the sequences of DYZ1 arrays amongst all the three sets of twins used in the present study. MZT1b showed loss of 35 bp compared to that in 1a, whereas 2a showed loss of 31 bp compared to that in 2b. Similarly, 3b showed 10 bp insertion compared to that in 3a. MZT1a germline DNA showed loss of 5 bp and 1b blood DNA showed loss of 26 bp compared to that of 1a blood and 1b germline DNA, respectively. Of the 69 restriction sites detected in DYZ1 arrays, MboII, BsrI, TspEI and TaqI enzymes showed frequent loss and or gain amongst all the 3 pairs studied. MZT1 pair showed loss/gain of VspI, BsrDI, AgsI, PleI, TspDTI, TspEI, TfiI and TaqI restriction sites in both blood and germline DNA. All the three sets of MZT showed differences in the number of DYZ1 copies. FISH signals reflected somatic mosaicism of the DYZ1 copies across the cells. CONCLUSIONS: DYZ1 showed both sequence and copy number variation between the MZT males. Sequence variation was also noticed between germline and blood DNA samples of the same individual as we observed at least in one set of sample. The result suggests that DYZ1 faithfully records all the genetical changes occurring after the twining which may be ascribed to the environmental factors.

Desulfurization of thianthrene by a Gordonia sp. IITR100.

Thianthrene (TA) was desulfurized by an isolated strain, Gordonia sp. IITR100. The reaction is accompanied with the formation of TA-sulfoxide, TA-sulfone and 2-phenylsulfanylphenol. The formed 2-phenylsulfanylphenol undergoes further oxidation to o-hydroxyphenyl phenylsulfone that accumulates as an end product. Metabolism of TA to TA-sulfone can also occur by E. coli-DszC i.e. E. coli cells that were harboring the gene coding for the enzyme dibenzothiophene desulfurase C. When presented to E. coli-DszC in a binary combination with dibenzothiophene, TA metabolism was completely inhibited. Metabolism of TA-TA-sulfone by E. coli-DszC, as well as the nature of metabolites formed by IITR100, suggests that the desulfurization pathway for TA is similar to that of the thiophenic compounds. This is first report on the desulfurization of thianthrene, and has implications on biodesulfurization when multiple sulfur compounds are present together.

Semiquinone fraction isolated from Bacillus sp. INM-1 protects hepatic tissues against γ-radiation induced toxicity.

Present study was focused on evaluation of a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 for its ability against γ radiation induced oxidative stress in irradiated mice. Animals were divided into four group, i.e., (i) untreated control mice; (ii) SQGD treated (50 mg/kg b. wt. i.p.) mice; (iii) irradiated (10 Gy) mice; and (iv) irradiated mice which were pre-treated (-2 h) with SQGD (50 mg/kg b. wt. i.p.). Following treatment, liver homogenates of the treated mice were subjected to endogenous antioxidant enzymes estimation. Result indicated that SQGD pre-treatment, significantly (P < 0.05) induced superoxide dismutase (SOD) (19.84 ± 2.18% at 72 h), catalase (CAT) (26.47 ± 3.11% at 12 h), glutathione (33.81 ± 1.99% at 24 h), and glutathione-S-transferase (24.40 ± 2.65% at 6 h) activities in the liver of mice as compared with untreated control. Significant (P < 0.05) induction in SOD (50.04 ± 5.59% at 12 h), CAT (62.22 ± 7.50 at 72 h), glutathione (42.92 ± 2.28% at 24 h), and glutathione-S-transferase (46.65 ± 3.25 at 12 h) was observed in irradiated mice which were pre-treated with SQGD compared with only irradiated mice. Further, significant induction in ABTS(+) radicals (directly proportional to decrease mM Trolox equivalent) was observed in liver homogenate of H2 O2 treated mice which were found to be significantly inhibited in H2 O2 treated mice pre-treated with SQGD. Thus, it can be concluded that SQGD treatment neutralizes oxidative stress caused by irradiation not only by enhancing endogenous antioxidant enzymes but also by improving total antioxidant status of cellular system and thus cumulative effect of the phenomenon may contributes to radioprotection.

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.

Assessing the multi-dimensional impact of lead-induced toxicity on collembola found in maize fields: From oxidative stress to genetic disruptions.

The prolonged exposure of agricultural soils to heavy metals from wastewater, particularly in areas near industrial facilities, poses a significant threat to the well-being of living organisms. The World Health Organization (WHO) has established standard permissible limits for heavy metals in agricultural soils to mitigate potential health hazards. Nevertheless, some agricultural fields continue to be irrigated with wastewater containing industrial effluents. This study aimed to assess the concentration of lead in soil samples collected from agricultural fields near industrial areas. Subsequently, we determined the lethal concentration (LC50) of lead (Pb) and other heavy metals for two Collembola species, namely Folsomia candida, a standard organism for soil ecotoxicity tests, and comparing it with Proisotoma minuta. The research further examined the toxic effects of lead exposure on these two species, revealing depletion in the energy reservoirs and alterations in the tissue histology of both organisms. The study revealed that lead can induce genotoxic damage as it evidently has moderate binding affinity with the ct-DNA and hence can cause DNA fragmentation and the formation of micronuclei. Elevated lipid peroxidation (LPO) levels and protein carbonylation levels were observed, alongside a reduction in antioxidant enzymes (CAT, SOD & GPx). These findings suggest that lead disrupts the balance between oxidants and the antioxidant enzyme system, impairing defense mechanisms and consequential derogatory damage within microarthropods. The investigation elucidates a complex network of various signaling pathways compromised as a result of lead toxicity. Hence, it presents a novel perspective that underscores the pressing necessity for implementing an integrated risk assessment framework at the investigated site.

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.

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.

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.

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.

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.

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.

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.