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SnO2-CeO2 nanocomposite materials (0.1SnO2–0.9CeO2, 0.15SnO2–0.85CeO2, 0.2SnO2–0.8CeO2, and 0.3SnO2–0.7CeO2) were prepared by co-precipitation in a water-isopropanol solution followed by thermal treatment. The materials were characterized by EDX, TEM, XRD and low-temperature nitrogen adsorption and used for comparative removing dye azorubine in water. It was shown that 0.15SnO2-0.85CeO2 solid solution; based on the crystal lattice of cerium dioxide; had a 15 mol % content of tin. The material was nearly spherical particles of size 8–10 nm. The adsorption followed Langmuir, Freundlich, Temkin, Flory-Higgins, Dubinin-Radushkevich isotherms and kinetics pseudo-first-order, pseudo-second-order, Elovich-Chen-Clayton, Boyd, and Vebber-Morris models. The Ho and Langmuir models were most adequately described the process of azorubine adsorption. The maximum adsorption of azorubine (96.1%) was achieved with 20 min of contact time, pH 6, azorubine concentration 20 mg/L and adsorbent dose 1.0 g/L. The regeneration of the adsorbent was achieved by catalytic oxidative destruction of azorubine with hydrogen peroxide. The reported adsorbent had an exceptional capability to remove azorubine in water with the loss of about 10 % adsorption capacity after running 6 times. The reported process may be assumed as an effective method for the removal of azorubine from water with the economy due to the absence of wastewater during the regeneration of the adsorbent.

Background Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cases. The matter of concern is more severe with very limited options of treatment and lack of new drugs, cisplatin and doxorubicin are the only two drugs mostly used in therapy. This situation along with the epidemiological data calls for the development of newer better and safer agents. Herein, we report nine novel benzothiazole derivatives based on structure-based drug discovery and molecular modelling approaches. Material and methods Newly designed compounds were synthesized following a four-step reaction and were characterized for structural confirmation. These novel compounds were evaluated on the MTT assay for their in vitro efficiency using the TCP1020 cell lines. These were further analysed for their mechanism of action based on in silico studies. Results Two compounds of the series exhibit promising results which are in agreement with the in-silico studies. It was found that the methyl group at the seventh position to the nitrogen decreases the electron affinity of the series and is thus responsible for the activity in 4e. The methyl substituted compound 4e and fluoro substituted compound 4i shows the highest activities with an IC50 of 10.1 ± 0.2 and 7.8 ± 0.7 respectively.

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

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

Chromium (Cr), Lead (Pb) and Cadmium (Cd) have been conceded as one of the most perilous heavy metals which causes a prominent affliction on both environment and human health. In this study, chemical modification of biodegradable, eco-friendly materials such as cellulose and chitosan were carried out to prepare a composite adsorbent and established an optimized condition for adsorption of heavy metal ions such as Cr, Pb and Cd from contaminated aqueous wastes. α-cellulose was treated with HCl and H2SO4 to have better adsorption properties. On the contrary, modification of chitosan was carried out by acetaldehyde solution and acetic acid. Composite adsorbent was obtained as a mixture, comprising of modified cellulose and chitosan in a specific proportion (2g:1g). The surface characteristics of treated cellulose, chitosan and composite sample were evaluated by FTIR and SEM analysis. In addition, batch adsorption experiments were carried out to measure the influences of pH of the solution, adsorbent dosage and the initial concentration of metal ions. The maximum removal efficiency of Cr, Pb and Cd by composites was 56, 85 and 94%, respectively, at pH 4 when the metal concentration and adsorbent dosage were 60 ​ppm and 1.0 ​g ​L−1. The maximum adsorption of Cr, Pb and Cd by composites was 55, 80 and 91 ​mg ​g−1, respectively, at pH 4 when the metal concentration and adsorbent dosage were 120 ​ppm and 1.0 ​g ​L−1.

The University of Pretoria Vice Chancellor's post-doctoral fellowship and the National Research Foundation (NRF), South Africa Innovation post-doctoral fellowship schemes.

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

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

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

A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results indicated that even though most of the synthesized compounds exhibited a good anticancer activity against various cancer cells in vitro, some of the compounds like 9e, 9g and 9q were found to be the most promising analogues in this series, with compound 9e showing IC50 values of 1.5 μM, 0.6 μM, 2.4 μM and 1.2 μM on PC-3, MCF-7, A-549 and HCT-116 cell lines respectively. Further, flow cytometry studies showed that MCF-7 cells treated with the compounds 9e, 9g and 9q were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. These lead molecules were further studied for NF-κB, p65 transcription factor inhibitory activity which confirmed concentration dependent inhibition against NF-κB, p65 with analogue 9e showing 57% inhibition at 2 μM, 9g showing 62% inhibition at 3 μM and 9q showing 54% inhibition at 2 μM concentration.

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