Applications of QSAR study in drug design of tubulin binding inhibitors.

New drug discovery is recognized as a complicated, costly, time-consuming, and difficult process. Computer-aided drug discovery has developed as a potent and promising method for faster, cheaper, and more effective drug creation. Recently, the rapid rise of computational methods for drug discovery, including anticancer medicines, had a substantial and exceptional impact on anticancer drug design, as well as providing beneficial insights into the field of cancer therapy. In this paper, we discussed the quantitative structure-activity relationship (QSAR), which is a significant in-silico tool in rational drug design. The QSAR method is used to optimize the existing leads to improve their biological activities, and physicochemical properties and to predict the biological activities of untested and sometimes unavailable compounds, so QSAR is a significant method in drug designing. This article is a comprehensive review of various QSAR studies conducted which help to create new and potent inhibitors for targeting tubulin, a crucial target in cancer treatment. It particularly focuses on studies that provide structural insights into the compounds targeting tubulin. It should prioritize continually researching specific scaffolds, with a focus on important attachment regions, to gather more powerful molecular data and enhance models. This will lead to a better understanding of drug interactions and the development of improved cancer-targeting inhibitors for tubulin.Communicated by Ramaswamy H. Sarma.

In silico homology modeling, docking and sequence analysis of some bacterial laccases to unravel enzymatic specificity towards lignin biodegradation.

Laccase is a delignifying enzyme that belongs to the oxidoreductase family, and it has long been investigated as a pretreatment agent in biofuel production. In this study, amino acid sequences of five bacterial laccases from Bifidobacterium breve, Klebsiella pneumonia, Pseudodesulfovibrio hydrargyri, Pseudomonas aeruginosa and Veillonella rodentium have been retrieved from UniProtKB for sequence alignment, phylogenetic analysis using MEGA 7.0 and 3 D structure prediction by homology modeling in SWISS-MODEL. Multiple sequence alignment between all the bacterial laccase sequences revealed a similar structural fold, although the overall protein sequence varied greatly with the substrate binding sites. Further molecular docking in AutoDock Vina and MD stimulation (MDS) in GROMACS for those modelled enzymes were performed considering both apo and ligand bound structures considering both apo and its ligand bound form. Investigation of molecular interaction utilizing docking of five bacterial laccases with three substrates (ABTS, DMP and Guaiacol) revealed that ABTS with K. pneumoniae laccase had the highest binding energy of -7.00 kcal/mol. In the current MDS investigation, bacterial laccases demonstrated greater binding and substrate energy in the ligand bound complex than in the apo form for ABTS, DMP and Guaiacol. In most cases of bacterial laccase, MDS revealed that DMP bound complex was more stable within an average RMSD value lower than 0.5 nm throughout 100 ns time scale. Thus, in silico studies undertaken in this work will be useful in determining the stable enzyme-substrate complex which further might improve the enzymatic catalysis of bacterial laccases for lignin breakdown and biofuel generation.

Anti-SARS-CoV-2 antibodies among vaccinated healthcare workers: Repeated cross-sectional study.

Background: Since the novel SARS-CoV-2 has been detected and the ensuing pandemic, the search for a cure or prevention has been the only target of the medical fraternity. As the second wave racked havoc, vaccines seemed to be the only viable option to stop this global surge. World Health Organization (WHO) and subsequently the Government of India have issued emergency use authorization to two vaccines. Our study aims to estimate the prevalence of the anti-SARS-CoV-2 antibodies and identify predictors of antibody titers in vaccinated healthcare workers in VIMSAR, Burla. Methods: This is a part of the ongoing, repeated cross-sectional study. Participants were enrolled well above the sample size (322) to increase precision. Two rounds of the survey were conducted and are being reported. Serum IgG antibodies against spike protein of SARS-CoV-2 were estimated using Elecsys® anti-SARS-CoV-2S is an immunoassay by ECLIA-based Cobas e411 analyzer. Univariate and multivariate regression were used in statistical analysis. Results: Our results show that 95.1% and 99.5% of the vaccinated individuals have developed antispike protein antibodies after the first and second doses, respectively. Previous COVID-19 infection was significantly correlated with antibody production, and age was negatively correlated. No difference was reported for sex, occupation, and diabetes. Conclusion: Our interim analysis report is coherent with the available literature and research regarding the high efficacy of the COVID-19 vaccine as far as seroconversion is concerned.

Polymer-Induced Emission-Active Fluorine-Embedded Carbon Dots for the Preparation of Warm WLEDs with a High Color Rendering Index.

Exploration of many strategies has continuously contributed to producing aggregation-induced red-emissive carbon dots (CDs). In this work, we designed fluorine-embedded (F-embedded) CDs from 1,2,4-triaminobenzene, thiourea, and ammonium fluoride (NH4F) exhibiting polymer-induced emission (PIE). The PIE phenomenon of fluorescent CDs is obtained in poly(vinyl alcohol) (PVA), showing emissions at 611 and 617 nm in the dispersed and solid states, respectively. The CDs exhibited a red shift of 28 nm in the PVA solution because PVA hydroxyl groups formed a robust bridge-like H-bonding network between CDs. The fluorine embedded in CDs enhanced the H-bond affinity toward PVA. It showed that this H-bond restricted the coupling of CDs' surface states and inhibited the nonirradiation transfer. For the solid state, surface PVA chains eliminated the π-π interaction of the conjugated core and constructed a self-quenching resistance polymeric system around CDs. As a result, CDs showed an unexpected red shift of fluorescence emission in PVA. Furthermore, white light-emitting diodes (WLEDs) have a correlated color temperature (CCT) of 5232 K, and a high color rendering index of 95 has been fabricated by integrating the red- and green-emissive films over the UV LEDs. Interestingly, the as-synthesized CDs showed room temperature phosphorescence (RTP), which enabled us to employ the CDs in double-security protection. Simultaneously, CDs have been used in fingerprint detection.

Effect of Solvent-Derived Highly Luminescent Multicolor Carbon Dots for White-Light-Emitting Diodes and Water Detection.

Recently, the multicolor fluorescent carbon dots (CDs) have drawn much attention due to their various applications. Herein, we report multicolor emissive CDs by solvent-controlled and solvent-responded approaches. The blue to red color emissive CDs are obtained by the solvothermal method by varying the solvent during the reaction. The red color emissive CDs (R-CDs) with good quantum yield is obtained in a water medium. The detailed characterization revealed that the solvent controls the particle size, band gap, and nitrogen doping concentration. Specifically, in the protic solvent, the high N content and presence of imine nitrogen are the reason for red emission. However, in an aprotic solvent, the least N doping and a lack of C-O groups are responsible for a blueshift. Interestingly, it was observed that the R-CDs provide a full range of visible color by dispersing in different immiscible solvents. The fluorescence emission in immiscible solvents is redshifted by enhancing the polarity. Moreover, the developed CDs detected the low water concentrations (≤0.2%, v/v) visually and fluorometrically in various organic solvents. Simultaneously, we have employed synthesized CDs in white-light-emitting diodes and fluorescent ink.

Facile Strategy to Synthesize Magnetic Upconversion Nanoscale Metal-Organic Framework Composites for Theranostics Application.

Recently, the design of a theranostics system has involved increasing attention in the area of biomedical applications. In many cases, the intricate synthesis process of upconversion nanoparticle-based composite materials limits the use of theranostics applications. To address this challenge, a nanocomposite has been successfully fabricated by the conjugation of magnetic NaGdF4:Yb/Er nanoparticles as an imaging agent and MIL-53(Fe) as a drug carrier through a single step. Simultaneously, folic acid is encapsulated on the surface of the nanocomposite by conjugation chemistry to achieve the targeted drug delivery applications. The synthesized nanocomposite exhibits a sufficient amount of loading ability toward the model anticancer doxorubicin and possesses pH-responsive drug release. The functionalized nanocomposite not only possesses excellent colloidal stability and good magnetic and fluorescence property but also shows superior biocompatibility, strong tumor cell growth inhibitory effect, and cancer-enhanced cellular uptake. It is expected that the synthesized nanocomposite can also serve as a platform for both T1 and T2 MRI contrast agents.

In situ synthesized lactobionic acid conjugated NMOFs, a smart material for imaging and targeted drug delivery in hepatocellular carcinoma.

Development of multifunctional nanoscale materials for targeted drug delivery in liver tumor cells has been realized in this work. Recently, nanoscale metal organic frameworks (NMOFs) have been used as a potential drug carrier for its unique characteristic properties. Here we have demonstrated a single step approach for the fabrication of lactobionic acid (LA) modified NH2-MIL-53(Al) NMOFs via green synthetic process. The anticancer drug doxorubicin (DOX) is loaded for targeted delivery in hepatocellular carcinoma cell lines (HepG2). The LA-targeted NMOFs have no cytotoxicity in both normal and hepatocellular cell lines. Human hepatocellular carcinoma cell lines are enriched of asialoglycoprotein receptors and simultaneously LA has strong recognition ability towards this receptor. The MTT assay reveals the DOX loaded LA-embedded NMOFs show greater cytotoxicity towards HepG2 cell lines in compare to normal cell lines. The FACS study also indicates that DOX-loaded LA-targeted NMOFs show greater cell death than bare NMOFs. More importantly, the NH2-MIL-53 NMOFs possess inherent fluorescent property and also the fluorescence intensity remains unaltered after conjugation of LA. So, the developed LA-embedded multifunctional NMOFs have good therapeutic efficacy for cell imaging and targeted drug delivery.

Facile synthesis of carbon fiber reinforced polymer-hydroxyapatite ternary composite: A mechanically strong bioactive bone graft.

Carbon fiber reinforced carboxymethyl cellulose-hydroxyapatite ternary composites have been synthesized by a simple wet precipitation method for weight bearing orthopedic application. Composites were synthesized with the incorporation of chemically functionalized carbon fibers. The functional groups onto the surface of fibers induced the formation of hydroxyapatite at the bridging position through which fibers were effectively bound with matrix. Consequently, the flexural strength and compressive strength of composite have reached to 140 MPa and 118 MPa, respectively. The flexural modulus of the composite is in the range of 9-22 GPa. In-vitro cell study showed that the composite possesses excellent cell proliferation and differentiation ability. With these excellent mechanical and biological properties, synthesized composite exhibits potential to be used as a mechanically compatible bioactive bone graft.

IRMOF-3: A fluorescent nanoscale metal organic frameworks for selective sensing of glucose and Fe (III) ions without any modification.

The amine functionalized isoreticular metal-organic framework-3 (IRMOF-3) is synthesized by hydrothermal method. Till now, it's widely used in the area of gas separation, adsorption, and catalysis due to large surface area, structural stability, and tunability. Here, we have reported the use of fluorescent nanoscale IRMOF-3 for highly selective detection of glucose as well as Fe3+ ions without any modification. This is due to NH2 and COOH groups are present on the surface of IRMOF-3 to bind cis-diols of the glucose molecule via host-guest interaction, and Fe3+ ions via ligand to metal charge transfer. The Synthesized IRMOF-3 has average diameter of 160 ±â€¯20 nm and interestingly possess deep blue fluorescent emission spectra at 460 nm with quantum yield 17.3%. Using fluorometric assay, the limit of detection (LOD) of glucose and Fe3+ ions was found to be 0.56 µM and 4.2 nM respectively. More importantly, the synthesized IRMOF-3 is also utilized for detection of glucose and Fe3+ ions in bio-environmental samples.

Fabrication of a Hierarchical TiO2 Microsphere/Carbon Dots Photocatalyst for Oxygen Evolution and Dye Degradation Under Visible Light.

Anatase hierarchical TiO2 microsphere/carbon dots composite (HTM/CDs) was fabricated by a facile method for active visible light photocatalysis. The phase, morphology, microstructure and optical properties were investigated by X-ray diffraction, scanning electronmicroscopy, transmission electron microscopy and UV-VIS diffuse reflectance spectroscopy respectively. Under visible light illumination, the fabricated HTM/CDs composite was exhibited an enhanced photo catalytic activity compared to that of pure hierarchical TiO2 microspheres (HTM). Such an enhancement in photocatalytic activity can be attributed to an increase in the absorption of visible light. The photocatalytic activity was investigated by the degradation of a model dyemalachite green (MG) and oxygen production through water splitting.We believe that this type of hybrid material could be used as a highly active and stable visible light photocatalyst to remove pollutants as well as energy production with high performance.

One pot synthesis of carbon dots decorated carboxymethyl cellulose- hydroxyapatite nanocomposite for drug delivery, tissue engineering and Fe3+ ion sensing.

In this work, carbon dots conjugated carboxymethyl cellulose-hydroxyapatite nanocomposite has been synthesized by one-pot synthesis method and used for multiple applications like metal ion sensing, osteogenic activity, bio-imaging and drug carrier. The structure and morphology of the nanocomposite were systematically characterized by FTIR, XRD, TGA, FESEM, TEM and DLS. Results clearly demonstrated the formation of fluorescent enabled carbon dots conjugated nanocomposite from carboxymethyl cellulose-hydroxyapatite nanocomposite by a simple thermal treatment. The synthesized nanocomposite is smaller than 100 nm and exhibits fluorescence emission band around 440 nm upon excitation with 340 nm wavelength. In the meantime, the nanocomposite was loaded with a chemotherapeutic drug, doxorubicin to evaluate the drug loading potential of synthesized nanocomposite. Moreover, the as-synthesized nanocomposite showed good osteogenic properties for bone tissue engineering and also exhibited excellent selectivity and sensitivity towards Fe3+ ions.

Fabrication of nitrogen- and phosphorous-doped carbon dots by the pyrolysis method for iodide and iron(III) sensing.

A facile and novel strategy to synthesize nitrogen- and phosphorous-doped carbon dots (NPCDs) by single step pyrolysis method is described here. Citric acid is used as carbon source and di-ammonium hydrogen phosphate is used as both nitrogen and phosphorous sources, respectively. Through the extensive study on optical properties, morphology and chemical structures of the synthesized NPCDs, it is found that as-synthesized NPCDs exhibited good excitation-dependent luminescence property, spherical morphology and high stability. The obtained NPCDs are stable in aqueous medium and possess a quantum yield of 10.58%. In this work, a new assay method is developed to detect iodide ions using the synthesized NPCDs. Here, the inner filter effect is applied to detect the iodide ion and exhibited a wide linear response concentration range (10-60 µM) with a limit of detection (LOD) of 0.32 µM. Furthermore, the synthesized NPCDs are used for the selective detection of iron(III) (Fe3+ ) ions and cell imaging. Fe3+ ions sensing assay shows a detection range from 0.2 to 30 µM with a LOD of 72 nM. As an efficient photoluminescence sensor, the developed NPCDs have an excellent biocompatibility and low cytotoxicity, allowing Fe3+ ion detection in HeLa cells.

One-pot synthesis of multifunctional nanoscale metal-organic frameworks as an effective antibacterial agent against multidrug-resistant Staphylococcus aureus.

Drug-resistant bacteria are an increasingly serious threat to global public health. In particular, infections from multidrug-resistant (MDR) Gram-positive bacteria (i.e. Staphylococcus aureus) are growing global health concerns. In this work, we report the first use of nanoscale metal-organic frameworks (NMOFs) coencapsulating an antibiotic (vancomycin) and targeting ligand (folic acid) in one pot to enhance therapeutic efficacy against MDR S. aureus. Zeolitic imidazolate framework (ZIF-8) NMOFs, which have globular morphologies coencapsulating vancomycin and folic acid, are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, ulltraviolet-visible spectroscopy, and dynamic light-scattering techniques. We determined that the presence of folic acid on the surface of the NMOFs is significant in the sense of effective uptake by MDR S. aureus through endocytosis. The functionalized NMOFs transport vancomycin across the cell wall of MDR S. aureus and enhance antibacterial activity, which has been confirmed from studies of the minimum inhibitory concentration, minimum bactericidal concentration, cytotoxicity of bacterial cells, and generation of reactive oxygen species. This work shows that functionalized NMOFs hold great promise for effective treatment of MDR S. aureus.

Nanostructured Fe3O4@Fe2O3/Carbon Dots Heterojunction for Efficient Photocatalyst Under Visible Light.

A facile method for the synthesis of porous magnetic nanoparticles (Fe3O4@Fe2O3) embedded with carbon dots (CDs) are demonstrated for photocatalysis study. Here, a simple, low-cost and green method is developed to synthesize CDs from natural source. The synthesized carbon dots are highly water soluble and monodisperse with particle size 2­5 nm. X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, UV-Vis absorption spectroscopy, BET surface area were employed to investigate the crystal structure, morphology, surface groups, optical properties, surface area of the synthesized nanocomposites. The photocatalytic performance of the nanocomposites was analyzed for the degradation of methylene blue under visible light and exhibited higher photocatalytic activity compared to Fe2O3 nanoparticles. Here the crucial role of CDs has been illustrated for the enhancement of photocatalytic activity.

One-pot synthesis of folic acid encapsulated upconversion nanoscale metal organic frameworks for targeting, imaging and pH responsive drug release.

In this work, a new theranostic nanoplatform is developed to construct an anticancer drug carrier by integrating the distinct advantages of upconversion nanoparticles (UCNPs) and metal organic frameworks (MOFs) encapsulated with a targeting ligand. Here NaYF4:Yb3+,Er3+ is chosen as an upconversion nanoparticle for its high luminescence properties. Then, folic acid encapsulated Zeolitic Imidazolate Framework-8 (ZIF-8) is directly coated on UCNPs in one step to form a monodispersed core-shell structured nanocomposite (labeled as UCNPs@ZIF-8/FA). The synthesized upconversion nanoscale MOFs (NMOFs) are simultaneously used as a targeted anticancer drug carrier and in cellular imaging. The UCNP@ZIF-8/FA nanocomposites are found to be nontoxic towards the human cervix adenocarcinoma (HeLa) and mouse fibroblast (L929) cell lines via a cell viability assay. It is worthwhile noting that, the anticancer drug 5-fluorouracil (5-FU) is absorbed into UCNP@ZIF-8/FA nanocomposites (loading amount 685 mg g-1) and also pH responsive drug release is observed. The as-prepared 5-FU loaded UCNP@ZIF-8/FA nanocomposites exhibited greater cytotoxicity towards HeLa cells due to the folate receptor-mediated endocytosis. Our study highlights the potential of developing multifunctional upconversion NMOFs for simultaneous targeted cellular imaging with delivery of anticancer drugs.

Carbon Dots Embedded Magnetic Nanoparticles @Chitosan @Metal Organic Framework as a Nanoprobe for pH Sensitive Targeted Anticancer Drug Delivery.

Recently, nanoscale metal organic frameworks (NMOFs) have been demonstrated as a promising carrier for drug delivery, as they possess many advantages like large surface area, high porosity, and tunable functionality. However, there are no reports about the functionalization of NMOFs, which combines cancer-targeted drug delivery/imaging, magnetic property, high drug loading content, and pH-sensitive drug release into one system. Existing formulations for integrating target molecules into NMOF are based on multistep synthetic processes. However, in this study, we report an approach that combines NMOF (IRMOF-3) synthesis and target molecule (Folic acid) encapsulation on the surface of chitosan modified magnetic nanoparticles in a single step. A noticeable feature of chitosan is control and pH responsive drug release for several days. More importantly, doxorubicin (DOX) was incorporated into magnetic NMOF formulation and showed high drug loading (1.63 g DOX g(-1) magnetic NMOFs). To demonstrate the optical imaging, carbon dots (CDs) are encapsulated into the synthesized magnetic NMOF, thereby endowing fluorescence features to the nanoparticles. These folate targeted magnetic NMOF possess more specific cellular internalization toward folate-overexpressed cancer (HeLa) cells in comparison to normal (L929) cells.

Magnetic nanoscale metal organic frameworks for potential targeted anticancer drug delivery, imaging and as an MRI contrast agent.

The development of a novel multifunctional porous nanoplatform for targeted anticancer drug delivery with cell imaging and magnetic resonance imaging has been realised in the current work. Here we have developed a magnetic nanoscale metal organic frameworks (NMOF) for potential targeted drug delivery. These magnetic NMOFs were fabricated by incorporation of Fe3O4 nanoparticles into porous isoreticular metal organic frameworks (IRMOF-3). To achieve targeted drug delivery towards cancer cells specifically, folic acid was conjugated to the NMOF surface. Then, the fluorescent molecule rhodamine B isothiocyanate (RITC) was conjugated to the NMOFs for biological imaging applications. The synthesized magnetic NMOFs were fully characterised by FTIR, powder XRD, XPS, SQUID, TGA, TEM, FESEM, and DLS. The synthesized magnetic NMOFs were observed to be smaller than 100 nm and were found to be nontoxic towards human cervix adenocarcinoma (HeLa) and murine fibroblast (NIH3T3) cells according to cell viability assays. The cancer chemotherapy drug paclitaxel was conjugated to the magnetic NMOFs through hydrophobic interactions with a relatively high loading capacity. Moreover, these folic acid-conjugated magnetic NMOFs showed stronger T2-weighted MRI contrast towards the cancer cells, justifying their possible significance in imaging.

Synthesis of highly fluorescent nitrogen and phosphorus doped carbon dots for the detection of Fe(3+) ions in cancer cells.

Highly fluorescent nitrogen and phosphorus-doped carbon dots with a quantum yield 59% have been successfully synthesized from citric acid and di-ammonium hydrogen phosphate by single step hydrothermal method. The synthesized carbon dots have high solubility as well as stability in aqueous medium. The as-obtained carbon dots are well monodispersed with particle sizes 1.5-4 nm. Owing to a good tunable fluorescence property and biocompatibility, the carbon dots were applied for intercellular sensing of Fe(3+) ions as well as cancer cell imaging.

Citric Acid Fuctionalized Magnetic Ferrite Nanoparticles for Photocatalytic Degradation of Azo Dye.

In this study different magnetic ferrite nanoparticles (MFe2O4, where M = Fe, Mn, Zn) were synthesized through an aqueous coprecipitation method and then functionalized with citric acid for the degradation of azo dye present in industrial waste water. Here we evaluated the role of citric acid for photocatalytic application. The synthesized nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and the catalytic activity in degradation of methyl orange (MO) was evaluated. The rate of MO degradation in different magnetic systems was determined by UV-Vis spectroscopy. The effect of active parameters (pH, initial MO concentration and effect of sunlight) on degradation performance was investigated. For the first time, citric acid chemistry is successfully exploited to develop a photocatalyst that can successfully degrade the dyes. This citric acid functionalized magnetic ferrite nanoparticles are very much effective for photocalytic degradation of dye and also these can be recollected with the help of permanent magnet for successive uses.

Single step synthesis of carbon dot embedded chitosan nanoparticles for cell imaging and hydrophobic drug delivery.

The florescent carbon dot conjugated chitosan nanoparticles are developed for the cellular imaging and delivery of poorly water soluble drug telmisartan (TEL). In this work, the florescent chitosan nanoparticles are synthesized in a single step. The presence of surface functional groups and conjugation of the nanoparticles are investigated by FTIR spectroscopy. Dynamic light scattering and TEM analysis are performed to determine the size of the nanoparticles. To investigate the surface morphology FESEM analysis is also performed. The cytotoxicity of the nanoparticles is examined by MTT assay using normal lymphocytes and KG1A cancer cell lines. The intracellular cellular uptake is studied by fluorescence microscopy and flow cytometry analysis. The interactions between the nanoparticles and the drug are investigated by Gaussian 09 and visualized by GaussView 5 program package.