Maximum Affinity Research Articles

Antihyperlipidemic studies of newly synthesized phenolic derivatives: in silico and in vivo approaches.

BackgroundHyperlipidemia is a worth-mentioning risk factor in quickly expanding cardiovascular diseases, including myocardial infarction and, furthermore, in stroke.MethodsThe present work describes the synthesis of phenolic derivatives 4a–e and 6a–c with the aim of developing antihyperlipidemic agents. The structures of the synthesized compounds were confirmed by spectroscopic data. The in silico docking studies were performed against human 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase enzyme (PDB ID: 1HWK), and it was observed that compounds 4a and 6a exhibited maximum binding affinity with target protein having binding energies −8.3 and −7.9 kcal, respectively.ResultsCompound 4a interacts with amino acids Val805 with distance 1.89 Å and Met656, Thr558, and Glu559 with bonding distances 2.96, 2.70, and 2.20 Å, respectively. The in vivo antihyperlipidemic activity results revealed that compound 4a indicated minimum weight increment, ie, 20% compared with 35% weight increment with standard drug atorvastatin during 6 weeks of treatment. Moreover, increment in high-density lipoprotein cholesterol and decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were more prominent in case of 4a compared to atorvastatin with P<0.05. The synthesized compounds were nontoxic and well tolerated because none of the mice were found to suffer from any kind of morbidity and death during 6 weeks of dosing.ConclusionBased on our pharmacological evaluation, we may propose that compound 4a may act as a lead structure for the design and development of more potent antihyperlipidemic drugs.

Screening of cell surface properties of potential probiotic lactobacilli isolated from human milk.

Evaluation of eleven candidate probiotic Lactobacillus strains isolated from human milk showed that some of the strains were well endowed with desirable cell surface and attachment attributes. The cell surface properties (hydrophobicity, auto-aggregation, attachment to collagen and HT-29 monolayer) of probiotic Lactobacillus species of human milk origin were compared with reference probiotic/ non-probiotic species and pathogenic strains. The bacterial adhesion to hydrocarbons (BATH) was determined using three aliphatic (Chloroform, n-Hexane and n-Octane) and two aromatic (Toluene and Xylene) solvents. Maximum affinity of Lactobacillus strains towards chloroform and toluene indicated the presence of low electron acceptor/ acidic surface components on cell surface of most of the strains. The highest value of per cent hydrophobicity was recorded with chloroform in HM1 (L. casei) (97·10 ± 3·35%) and LGG (98·92 ± 1·24%). A moderate auto-aggregation attribute was observed in all of our Lactobacillus isolates. Only HM10, HM12 and HM13 exhibited comparatively enhanced precipitation rate after 7 h of incubation period. The adhesion potential to collagen matrix was highest in LGG (26·94 ± 5·83%), followed by HM1 (11·07 ± 3·54%) and HM9 (10·85 ± 1·74%) whereas, on HT-29 cells, HM8 (14·99 ± 3·61%), HM3 (13·73 ± 1·14%) and HM1 (11·21 ± 3·18%) could adhere effectively. In this manner, we noticed that although the cell surface properties and adhesion prospective of probiotic bacteria were strain dependent, five of our isolates viz. HM1, HM3, HM8, HM9 and HM10 exhibited promising cell surface properties, which could be further targeted as indigenous probiotic.

Synthesis, crystal structure, DNA binding and in vitro cytotoxicity studies of Zn(II) complexes derived from amino-alcohol Schiff-bases

Three new zinc(II) complexes, namely, [Zn2(H2L1)2(OAc)2] (1), [Zn3(H2L1)2(OAc)4] (2) and {[Zn3(H2L2)2(OAc)4]·C2H5OH·DMF} (3) [(H3L1 = Schiff-base derived from salicylaldehyde and 2-amino-2-ethyl-1,3-propanediol and H3L2 = Schiff-base derived from 5-chlorosalicylaldehyde and 2-amino-2-ethyl-1,3-propanediol)], were synthesized and characterized using elemental analyses, infrared spectroscopy and X-ray diffraction. Single crystal structure analysis reveals that complex 1 is five-coordinated distorted square pyramidal configuration. Complexes 2 and 3 exhibit the similar trinuclear structure. And the alkoxy groups in the ligands are play an important role in the formation of supramolecular networks of complexes 1–3. The interaction of the complexes 1–3 with calf thymus (CT) DNA was investigated using UV–visible (UV–Vis), circular dichroism spectra (CD), fluorescence, viscosity and thermal denaturation methods. The intrinsic binding constants for the complexes are found to order of 104 indicating that the complexes are good metallo-intercalators. Complex 1 shows maximum binding affinity (Kb: 7.64 × 104) compared to others. The all complexes can bind to CT-DNA via intercalative mode. The MTT assay show that the cytotoxicity of dinuclear complex 1 is more effective with HeLa cancerous cells. All the experimental results are suggestive that the nuclearity and configuration of zinc complexes have significant influence on their properties.

Influence of ethanol and temperature on adsorption of flavor-active esters on hydrophobic resins

Abstract Flavor-active esters, produced during fermentation, are vital components and important contributors to the aroma of beer. In order to separate trace amounts of esters, their adsorption behavior in the presence of high concentrations of ethanol and their thermodynamic behavior under the influence of temperature needs to be understood. This study reports the influence of temperature on single component adsorption isotherms of four esters (i.e. ethyl acetate, isopentyl acetate, ethyl 4-methylpentanoate, and ethyl hexanoate) on two hydrophobic resins (i.e. Amberlite XAD16N, and Sepabeads SP20SS) and the estimation of heat, entropy, and Gibbs energy of adsorption. Higher heat and entropy of adsorption are obtained for ethyl hexanoate and ethyl 4-methylpentanoate in comparison, due to their higher hydrophobicity, stronger binding, and the exothermic nature of their adsorption. A higher concentration of ethanol (tested from 1 to 30% (v/v)), lowers the activity coefficient of esters in the aqueous phase, and subsequently lowers adsorption and Langmuir affinity parameters. Increase of temperature from 284.15 to 325.15 K shows a reverse influence on maximum adsorption capacity and Langmuir affinity parameters. Langmuir affinity parameters are obtained at various ethanol concentrations and temperatures. The reported parameters and thermodynamic properties in this paper, are essential for designing an industrial scale adsorption step for separation of flavor-active esters under non-isothermal conditions.

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (−6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Diorganotin(IV) complexes (1‐4) of MESNA (sodium 2‐mercaptoethanesulfonate HSCH2CH2SO3Na) and a mixed ligand complex of dibutyltin(IV), 1,10‐phenanthroline and MESNA (5) were synthesized with thermal and microwave assisted methods. All the complexes were characterized thoroughly with the help of analytical and various spectroscopic techniques viz. FTIR, NMR (1H, 13C, and 119Sn NMR) spectroscopy and ESI‐MS spectrometery. Various spectrophotometric studies were carried out to decipher the binding mode of MESNA and its diorganotin complexes 1‐5 with calf thymus DNA (CT DNA) and thus, to calculate the binding constant (Kb). Absorption spectrophotometric study confirmed the interaction is through partial intercalation of all the complexes including MESNA, inside the DNA helix and calculated binding constant (Kb) is in the order of 103 M‐1. A series of emission spectrophotometric experiments support the results obtained through the absorption spectrophotometric studies. Circular dichroic (CD) spectroscopic analysis and viscosity measurement of CT DNA further complemented the fact that the partial intercalation plays a major role in the interaction of the studied complexes with CT DNA. All the studies corroborated that complex 2 bound to CT DNA with maximum affinity followed by complex 5 among all the complexes. Involvement of hydroxyl radicals as an active species in the cleavage activity of pBR322 plasmid DNA is proved by carrying out agarose gel electrophoretic technique.

Cost-Efficient and Robust On-Demand Video Transcoding Using Heterogeneous Cloud Services

Video streams usually have to be transcoded to match the characteristics of viewers' devices. Streaming providers have to store numerous transcoded versions of a given video to serve various display devices. Given the fact that viewers' access pattern to video streams follows a long tail distribution, for the video streams with low access rate, we propose to transcode them in an on-demand manner using cloud computing services. The challenge in utilizing cloud services for on-demand video transcoding is to maintain a robust QoS for viewers and cost-efficiency for streaming service providers. To address this challenge, we present the Cloud-based Video Streaming Services (CVS2) architecture. It includes a QoS-aware scheduling that maps transcoding tasks to the VMs by considering the affinity of the transcoding tasks with the allocated heterogeneous VMs. To maintain robustness in the presence of varying streaming requests, the architecture includes a cost-efficient VM Provisioner. This component provides a self- configurable cluster of heterogeneous VMs. The cluster is reconfigured dynamically to maintain the maximum affinity with the arriving workload. Results obtained under diverse workload conditions demonstrate that CVS2 architecture can maintain a robust QoS for viewers while reducing the incurred cost of the streaming service provider up to 85%

Design, synthesis, characterization and computational docking studies of novel sulfonamide derivatives.

This study reports three novel sulfonamide derivatives 4-Chloro-N-[(4-methylphenyl) sulphonyl]-N-propyl benzamide (1A), N-(2-hydroxyphenyl)-4-methyl benzene sulfonamide (1B) and 4-methyl-N-(2-nitrophenyl) benzene sulfonamide (1C). The compounds were synthesised from starting material 4-methylbenzenesulfonyl chloride and their structure was studied through 1H-NMR and 13C-NMR spectra. Computational docking was performed to estimate their binding energy against bacterial p-amino benzoic acid (PABA) receptor, the dihydropteroate synthase (DHPS). The derivatives were tested in vitro for their antimicrobial activity against Gram+ and Gram- bacteria including E. coli, B. subtilis, B. licheniformis and B. linen. 1A was found active only against B. linen; 1B was effective against E. coli, B. subtilis and B. linen whereas 1C showed activity against E. coli, B. licheniformis and B. linen. 1C showed maximum activity with minimum inhibitory concentration (MIC) of 50, 100 and 150 µg/mL against E. coli, B. licheniformis and B. linen respectively. 1C exhibited maximum affinity to DHPS with binding free energy of -8.1 kcal/mol. It enriched in the top 0.5 % of a library of 7663 compounds, ranked in order of their binding affinity against DHPS. 1C was followed by 1B which showed a moderate to low level MIC of 100, 250 and 150 µg/mL against E. coli, B. subtilis and B. linen respectively, whereas 1A showed a moderate level MIC of 100 µg/mL but only against B. linen. These derivatives may thus serve as potential anti-bacterial alternatives against resistant pathogens.

Incremental Graph Embedding Based on Spatial-Spectral Neighbors for Hyperspectral Image Classification

Recently, graph embedding-based methods have been developed in dimensionality reduction (DR) and classification of hyperspectral image (HSI). The key step for graph embedding methods is the construction of graph. The commonly used method is to manually choose nearest neighbors and then, compute edge weights using the spectral feature. However, the adjacency graph is inappropriate due to the negligence of spatial information. What is more, the construction of graph only takes training samples or $k$ nearest neighbors into account, which may lead to unsuitable graph representation. In this paper, we propose a novel incremental graph embedding (IGE) algorithm to construct a spatial-spectral neighbor graph for the HSI classification. The IGE can spread the discrimination information contained in training samples to their neighbors until each testing sample has a pseudo label. The spatial affinity weights between unlabeled data points and their labeled neighbors are calculated according to the construction strategies of the spatial-spectral neighbor graph. The pseudo label of the unlabeled data point is determined based on the maximum spatial affinity weights. Moreover, three weight strategies are designed for those samples nearby the decision boundary to improve the separability of different classes. In addition, the window size of spatial neighbors is able to be adjusted adaptively according to whether labeled data points in spatial neighbors exit. Experimental results on two datasets, Indian Pine and Pavia University have demonstrated that our algorithm is remarkably superior to other conventional DR algorithms on improving classification performance.

Pranlukast; An Alternative Potential Leptin Stimulator: Structure-Based Virtual Screening Study

Background: Leptin is secreted by adipocytes, transported into the brain and binds to its receptor in the hypothalamus, and activates JAK-STAT3, leading to increase in “anorexigenic peptides” which normally inhibit food consumption and reduce weight.Objectives: In the current study, a hybrid approach of molecular docking and virtual screening was performed, for the identification of active alternative compounds to manage obesity disorders.Methods: Screening was performed using structure-based drug design against approved FDA drugs; molecular modeling was done using AutoDockVina; only top 10 conformers’ ligands with highest and best scores were selected. In order to increase the likelihood of successful docking, in silico Virtual Screening (VS) of selected compounds were filtered according to their molecular weight and partition coefficient; a molecular weight of less than 500 and a partitioning coefficient (log P) of less than 5 filtering is applied.Result: Here, we report the screening of four compounds that have showed maximum binding affinity against Leptin receptor, obtained through the ZINC database. A VS approach coupled with docking energies illustrated that Pranlukast could be potential stimulator compounds for targeting Leptin receptor.Conclusion: We proposed that Pranlukast may be more potent Leptin receptor stimulator analogue based on the binding energy values. Further work can be extended to study the receptor ligand interactions experimentally and evaluation of their biological activity would help in designing novel therapeutic lead for the management of obesity disorders.

Attenuated Total Reflectance Fourier Transformation Infrared spectroscopy fingerprinted online monitoring of the kinetics of circulating Butyrylcholinesterase enzyme during metabolism of bambuterol

We have described a continuous flow ATR-FTIR method for measuring some of the Butyrylcholinesterase enzyme kinetics (Km and Vmax). This is done by developing a circulating system to be close as much as possible to the human circulation using human serum as a source of the enzyme with adjusted pH, isotonicity and temperature to give the maximum affinity of the enzyme towards its substrate (bambuterol).The experiment was running continuously for 90 min to monitor the production of terbutaline from the zero time of its appearance with a measured spectrum in each minute using ZnSe prism. The method was selective and successful for determination of Vmax to be 8.16 × 10−8 mol/min/ml and Km to be 2.28 × 10−5 mol, showing high affinity of the enzyme towards its prodrug substrate Bambuterol.This study critically probes the quantitative ability of the ATR-FTIR method for terbutaline, which was validated according to ICH guidelines showing high accuracy 100.39% and high selectivity towards the produced terbutaline, as the produced spectrums considered as fingerprint of each compound.

Schizonticidal antimalarial sesquiterpene lactones from Magnolia champaca (L.) Baill. ex Pierre: microwave-assisted extraction, HPTLC fingerprinting and computational studies

The present study explored the schizonticidal potential of traditionally used Magnolia champaca (L.) Baill. ex. Pierre flowers, identifying constituents of interest. The extraction of phytoconstituents was carried out by microwave-assisted technique, isolated via column chromatography, and characterised by various physicochemical, spectral (IR, 1H-NMR and Mass) and chromatographic (HPTLC) techniques. Both the isolated compounds (parthenolide and costunolide diepoxide) exhibited potent schizonticidal antimalarial activity during primary screening in rodent models, with maximum parasitaemia suppression (85.18% and 83.65%, respectively) at a dose of 20 mg/kg body weight when compared to the standard drugs chloroquine and artesunate. In silico techniques were employed to identify the probable biological target and mechanism of action of these isolated compounds. Molecular docking studies also predicted the binding orientations and multi-targeted action of these compounds, in particular costunolide diepoxide with maximum affinity towards SERCA and DHFR proteins. Additionally, favourable in silico ADMET parameters were envisaged through various computational programmes.

Biosorption of azo-dye using marine macro-alga of Euchema Spinosum

A study on various biosorbents in promoting environmental and economic sustainability has become a current attempt by researchers for removal of synthetic dye from industries. Marine algae are listed as excellent candidates for alternative biosorbents. Therefore, in this study, five indigenous species of marine macro-algae from a group of red, green and brown were investigated for their potential of removing azo-dye, Methylene Blue (MB) in aqueous solution. The best biosorbent was evaluated based on their maximum biosorption capacity (qmax) and affinity (b). Characterization of potential algae was determined by points zero charge (pHpzc), Fourier transform infrared spectroscopy (FT-IR) and Scanning electron microscope with Energy Dispersive X-Ray Analysis (SEM-EDX). It was further examined for the effect of various operational parameters such as pH (2–11), biosorbent dosage (0.2–1.2g/L) and initial concentration (50–200mg/L). The result reveals that the equilibrium time for all algae species can be reached within 60–80min at 27°C. At lower MB initial concentration (<1000mg/L), Euchema Spinosum (E. spinosum) performed the highest qmax and b, therefore it has been chosen as potential biosorbent. Experimental data were compiled well with Langmuir and Freundlich isotherm with R2=0.99. According to Langmuir model, the maximum homogenous biosorption capacity, qmax is 833.33mg/g and affinity, b, is 0.016. The kinetic data were better fitted to the pseudo-second-order kinetic model.

Expression dynamics of the REL, RELA, and IRF1 transcription factors in U937 macrophages after dioxin exposure

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is involved in a wide range of critical cellular events in response to endogenous signals or xenobiotics. 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) is one of the AhR ligands with the maximum affinity for AhR. TCDD is the most toxic among the dioxin xenobiotics and induces a wide range of biological responses, including immunotoxicity and cancer. The complex ligand:AhR:ARNT functions as a transcription factor, binding to the dioxin responsive element (DRE) sequences in the regulatory regions of target genes. Macrophages are key regulators of the innate immune response and being present in all body organs and tissues, they are one of the cell types that are the first to encounter xenobiotics; thus, the insight into the TCDD effect on macrophages is of paramount importance. Putative DREs are predicted using the SITECON software tool in the regulatory regions of the genes encoding transcription factors REL, RELA, and IRF1, expressed in macrophages. The nuclear extract and total RNA are isolated from the U937 macrophage-like cells exposed to 10 nM TCDD (or 0.1% DMSO as the control) for 1, 3, and 6 h. The binding of the TCDD:AhR:ARNT transcription complex from the nuclear extract with double-stranded oligonucleotides containing the putative DREs was studied by the EMSA. Quantitative real-time PCR demonstrates that the expression of these genes in the U937 macrophages increases in a statistically significant manner 1 h (the characteristic time of the maximal dioxin:AhR:ARNT translocation to the nucleus) after exposure to 10 nM TCDD. These results confirm the functional activity of the DREs residing in the IRF1, REL, and RELA regulatory regions via the AhR signaling pathway.

Role of leucine rich repeat and Ig domain containing 1 (LINGO1) in demyelinating and neurological diseases and investigation of conserved residues by docking analysis for novel therapeutic options

A demyelinating sickness is any ailment of the nervous system in which the myelin casing of neurons is injured. This harm weakens the transmission of signals in the pretentious nerves. Demyelinating diseases, like multiple sclerosis (MS) and Charcot-Marie-Tooth (CMT) disease, are categorized on the basis of the scratch of the myelin covering around neurons, because of swelling and gliosis in the central nervous system (CNS) and peripheral nervous system (PNS), respectively. In this current research, an amalgam approach of comparative modeling and molecular docking pursued by inhibitor recognition and structure modeling was used. Existing treatments mark anti-inflammatory ways to hinder or slow disease sequence. The recognition of a means to improve axon myelination would present innovative remedial approaches to restrain and probably turn around disease progression. A computational ligand-target docking method was applied to investigate structural composites of the Leucine Rich Repeat and Ig Domain Containing 1 (LINGO1) with three ligands to understand the structural foundation of this protein goal specificity. The following ten residues were conserved for all the three ligands interaction LEU133, ILE134, Pro135, LEU136, ILE155, ILE157, LEU159, ASP160, TYR161, and MET162 which are present in Leucine Rich Repeat 3 and 4 domains. Therefore, these three ligands can be utilized as the potential inhibitors to prevent various neurological disorders and the axonal neuropathies especially the CMT disease. Docking analysis showed that the two important drugs which are widely used have the potential to block the Rho-Rock pathways. Here, we report inhibitors which showed maximum binding affinity for the three most important axonal regeneration inhibitors. However, further studies are required to find the applications of these drugs. Key words: Demyelination, RTN4, CMT1A, spinal cord injury, ROCK inhibition, neurite growth inhibitors.

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies.

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver—Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.

Nutritional, functional, phytochemical and structural characterization of gluten-free flours

Different gluten-free flours from various sources may vary in composition and properties, thereby affecting applications in food systems. Various gluten-free flours viz. sorghum, rice, moong, water chestnut flour (WCF) and unripe banana flour (UBF) were studied in comparison with wheat flour. These were studied for their proximate composition, pH, iodine affinity value, leaching, functional properties, phytochemical analysis, color analysis, and X-ray diffraction analysis. Protein content in these flours ranged from 5.31 to 24.07%moong flour having highest protein content. Variations were observed with fat percentage from 1.01 to 3.45%. All flours were high in carbohydrate content i.e. ranged between 61.63 to 81.19%. pH values indicated slight acidic nature of all flours. UBF was found to have maximum iodine affinity value (46086 ppm). Leaching study indicated the extent of leaching with respect to time in these flours. Light transmittance was decreased with the duration of cooking for all flours. Color analysis values showed the difference in the L*, a, b values. X-ray diffractograms revealed the crystallinity patterns of the flours with percentage crystallinity which ranged from 22.6 to 34.9.This study concludes that wheat can be substituted by these flours in various applications.

Pharmacoinformatics, Adaptive Evolution, and Elucidation of Six Novel Compounds for Schizophrenia Treatment by Targeting DAOA (G72) Isoforms.

Studies on Schizophrenia so far reveal a complex picture of neurological malfunctioning reported to be strongly associated with DAOA. Detailed sequence analyses proved DAOA as a primate specific gene having conserved gene desert region on both upstream and downstream region. The analyses of 10 MB chromosomal region of primates, birds, rodents, and reptiles having DAOA evidenced the conserved part in primates and in the rest of species, while DAOA is only present in primates. DAOA has four isoforms having one interaction partner DAO. Protein-protein analyses of four DAOA isoforms with DAO were performed individually and find potential interacting residues computationally. It was observed that molecular docking of approved FDA drugs revealed efficient results but there was no common drug with effective binding to all DAOA isoforms. Library of compounds was constructed by virtual screening of 2D similarity search against recommended SZ drugs in conjunction with their physiochemical properties. Molecular docking resulted in six novel compounds exhibiting maximum binding affinity with selected four DAOA isoforms. However not the entire schizophrenic population responds to the single drug and interestingly in this study six novel compounds having promising results and same binding site to that DAOA that may be used to interact with DAO against four DAOA isoforms were observed.

Synthesis, characterization, cytotoxic screening, and density functional theory studies of new derivatives of quinazolin-4(3H)-one Schiff bases.

A series of novel derivatives of quinazolinone Schiff bases were synthesized from benzoic acid starting material and evaluated for potential cytotoxic activities against the human breast adenocarcinoma (MCF-7) and the human colon adenocarcinoma (HT-29) cell lines. Compared to the reference drug, these compounds showed good cytotoxic activities against studied cell lines especially compounds 4d and 4e. The ground-state geometries of these compounds (4a-g) were optimized at the B3LYP/6–31G* density functional theory (DFT) level. Then maximum absorptions electron affinity, ionization potential, electronegativity (χ), energy gap (Egap), hardness (η), softness (S), electrophilicity (ω), and electrophilicity index (ωi) were calculated and discussed. The quantitative structure-activity relationship (QSAR) properties including the physicochemical parameters were also evaluated and studied. The computed properties of our novel synthesized compounds were compared with erlotinib compound.

GC-MS analysis and in-silico antipsychotic activity of Morinda citrifolia (Indian Noni)

GC-MS determination of bioactive components of Erythropalum scandens Bl., Bijdr.Sutha .S, Kalpana Devi .V, Mohan .V.R