Topoisomerases are nuclear enzymes that regulate topology of DNA by facilitating the temporary cleavage and ligation cycle of DNA. Among all forms of topoisomerases, TOP-IIA is extensively associated with cell proliferation and therefore is an important therapeutic target in diseases that involved cellular proliferation such as cancers. Nearly half of present-day antitumor regimens contain at least one prescription that act as a topoisomerase inhibitor. Generally, tumor cells show divergent expression of TOP-IIA compared to normal cells. The remarkable expression of TOP-IIA in various carcinomas provides a significant biomarker toward understanding the nature of malignancy. TOP-IIA expression and amplification studies help in diagnosing cancer and to observe the disease progression, overall survival (OS) of patients, and response to therapy. This review highlights the research output and analysis in exploring the standing of TOP-IIA in various carcinomas. As some reports show contradiction within the same field of interest, the outline of that may help to induce researchers for further investigation and clarification. To the best of our knowledge, this is the first overview briefly summarizing the prognostic feature of TOP-IIA in various types of cancer.
The large stomach worm, Haemonchus contortus is an important pathogen of goats (Capra hircus) and sheep (Ovis aries). This paper describes characteristics of surface cuticular ridges (synlophe) of H. contortus adults from the two hosts. There were more ridges in H. contortus from goats compared to that from sheep. Total body length, vulvar morphology, spicule length and cervical papillae had been considered as markers of physical adaptation and were studied and described.
Tyrosine kinase overexpression could result in an unfavourable consequence of cancer progression in the body. A number of kinase inhibitor drugs targeting various cancer-related protein kinases have been developed and proven successful in clinical therapy. Benzimidazole is one of the most studied scaffolds in the search for effective anticancer drugs. The association of various functional groups and the structural design of the compounds may influence the binding towards the receptor. Despite numerous publications on the design, synthesis and biological assays of benzimidazole derivatives, their inhibitory activities against epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), have not been specifically analysed. This review covers recent research reports on the anticancer activity of benzimidazole derivatives focusing on EGFR expression cell lines, based on their structure-activity relationship study. We believe it would aid researchers to envision the challenges and explore benzimidazole's potentials as tyrosine kinase inhibitors.
The lack of stability is a challenge for most heterogeneous catalysts. During operations, the agglomeration of particles may block the active sites of the catalyst, which is believed to contribute to its instability. Recently, titanium oxide (TiO2) was introduced as an alternative support material for heterogeneous catalyst due to the effect of its high surface area stabilizing the catalysts in its mesoporous structure. TiO2 supported metal catalysts have attracted interest due to TiO2 nanoparticles high activity for various reduction and oxidation reactions at low pressures and temperatures. Furthermore, TiO2 was found to be a good metal oxide catalyst support due to the strong metal support interaction, chemical stability, and acid-base property. The aforementioned properties make heterogeneous TiO2 supported catalysts show a high potential in photocatalyst-related applications, electrodes for wet solar cells, synthesis of fine chemicals, and others. This review focuses on TiO2 as a support material for heterogeneous catalysts and its potential applications.
During the process and operation of the dyes, the wastes produced were commonly found to contain organic and inorganic impurities leading to risks in the ecosystem and biodiversity with the resultant impact on the environment. Improper effluent disposal in aqueous ecosystems leads to reduction of sunlight penetration which in turn diminishes photosynthetic activity, resulting in acute toxic effects on the aquatic flora/fauna and dissolved oxygen concentration. Recently, photodegradation of various synthetic dyes has been studied in terms of their absorbance and the reduction of oxygen content by changes in the concentration of the dye. The advantages that make photocatalytic techniques superior to traditional methods are the ability to remove contaminates in the range of ppb, no generation of polycyclic compounds, higher speed, and lower cost. Semiconductor metal oxides, typically TiO2, ZnO, SnO, NiO, Cu2O, Fe3O4, and also CdS have been utilized as photocatalyst for their nontoxic nature, high photosensitivity, wide band gap and high stability. Various process parameters like photocatalyst dose, pH and initial dye concentrations have been varied and highlighted. Research focused on surface modification of semiconductors and mixed oxide semiconductors by doping them with noble metals (Pt, Pd, Au, and Ag) and organic matter (C, N, Cl, and F) showed enhanced dye degradation compared to corresponding native semiconductors. This paper reviews recent advances in heterogeneous photocatalytic decolorization for the removal of synthetic dyes from water and wastewater. Thus, the main core highlighted in this paper is the critical selection of semiconductors for photocatalysis based on the chemical, physical, and selective nature of the poisoning dyes.
A total of 234 samples of food, consisting of 158 of raw and 76 samples of ready-to-eat food were examined for the presence of Listeria monocytogenes. The frequencies of L. monocytogenes contamination in raw foods were: chicken portions (60%), liver (60%) and gizzard (62%), beef (50%), beansprout (85%), prawns (44%), kupang (dried oysters) (33%), bean cake (25%), satay (48%) and leafy vegetables (22%). Of the ready-to-eat foods: satay (26%), prawns, squids, clams and chicken dishes (22%), cucumber (80%) and peanut sauce (20%) were found to yield L. monocytogenes.
A series of novel 1-(2'-α-O-D-glucopyranosyl ethyl) 2-arylbenzimidazoles has been prepared via one-pot glycosylation of ethyl-1-(2'-hydroxyethyl)-2-arylbenzimidazole-5-carboxylate derivatives. Synthesis of the 2-arylbenzimidazole aglycones from 4-fluoro-3-nitrobenzoic acid was accomplished in four high-yielding steps. The reduction and cyclocondensation steps for the aglycone synthesis proceeded efficiently under microwave irradiation to afford the appropriate benzimidazoles in excellent yields within 2-3 min. Glycosylation of the hydroxyethyl aglycones with the perbenzylated 1-hydroxy- glucopyranose, pretreated with the Appel-Lee reagent, followed by catalytic hydrogenolysis delivered the desired 1-(2'-α-O-D-glucopyranosyl ethyl) 2-aryl-benzimidazoles in a simple and straightforward manner.
Targeted drug delivery system improves the efficiency and safety of the therapeutic agents by managing the pharmacokinetics and pharmacodynamics of drugs. Currently, numerous drug carrier systems have been developed with different sizes, architectures and characteristics surface properties. Among different systems, macromolecules have a wide range of applications in targeted drug delivery system. The optimal drug loading potential, smooth drug releasing ability and biocompatibility are the distinguishing features that ensure the drugs delivery ability of macromolecules. This review briefly introduces some of the most commonly studied macromolecules which have been recommended as drugs delivery vehicles.
An alkaloid from Maclurodendron porteri has been isolated and characterized. Extraction process was conducted by acid-base extraction method followed by column chromatography. The structure was established by nuclear magnetic resonance spectroscopy and mass spectrometry. The compound was identified as haplophytin B which occurs commonly in the Rutaceae family. However, this is the first time this alkaloid was isolated and reported from the species. The compound showed no inhibition against Staphylococus aureus, Pseudomonas aeruginosa, Bacillus cereus and Escherichia coli and no cytotoxic activity against H199 and A549 cell lines.
The pig (Sus scrofa) mitochondrial genome was targeted to design short (15-30 nucleotides) DNA markers that would be suitable for biosensor-based hybridization detection of target DNA. Short DNA markers are reported to survive harsh conditions in which longer ones are degraded into smaller fragments. The whole swine mitochondrial-genome was in silico digested with AluI restriction enzyme. Among 66 AluI fragments, five were selected as potential markers because of their convenient lengths, high degree of interspecies polymorphism and intraspecies conservatism. These were confirmed by NCBI blast analysis and ClustalW alignment analysis with 11 different meat-providing animal and fish species. Finally, we integrated a tetramethyl rhodamine-labeled 18-nucleotide AluI fragment into a 3-nm diameter citrate-tannate coated gold nanoparticle to develop a swine-specific hybrid nanobioprobe for the determination of pork adulteration in 2.5-h autoclaved pork-beef binary mixtures. This hybrid probe detected as low as 1% pork in deliberately contaminated autoclaved pork-beef binary mixtures and no cross-species detection was recorded, demonstrating the feasibility of this type of probe for biosensor-based detection of pork adulteration of halal and kosher foods.
A test for assessing pork adulteration in meatballs, using TaqMan probe real-time polymerase chain reaction, was developed. The assay combined porcine-specific primers and TaqMan probe for the detection of a 109 bp fragment of porcine cytochrome b gene. Specificity test with 10 ng DNA of eleven different species yielded a threshold cycle (Ct) of 15.5 ± 0.20 for the pork and negative results for the others. Analysis of beef meatballs with spiked pork showed the assay can determine 100-0.01% contaminated pork with 102% PCR efficiency, high linear regression (r(2) = 0.994) and ≤ 6% relative errors. Residuals analysis revealed a high precision in all determinations. Random analysis of commercial meatballs from pork, beef, chicken, mutton and goat, yielded a Ct between 15.89 ± 0.16 and 16.37 ± 0.22 from pork meatballs and negative results from the others, showing the suitability of the assay to determine pork in commercial meatballs with a high accuracy and precision.
Calixarene derivatives are reported as potential therapeutic agents. Azo derivatives of calixarenes have not been given much consideration to explore their biomedical applications. In the present study, some azo-based derivatives of calix[4]arene were synthesized and characterized and their antibacterial and antiviral potentials were studied. The mono azo products of sulphanilamide, sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against bacterial strains with minimum inhibition concentration values ranging from 0.97 to 62.5 μg/mL. For mono azo products, the diazotized salt was applied as a limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3 (molar ratio) helped in partial substitution. Molecular docking was performed to see the interaction of the designed compounds with two bacterial and one viral (neuraminidase) receptor. Some of the derivatives showed good interaction with the active site of bacterial and neuraminidase enzymes through hydrogen, hydrophobic and pi-pi interactions, and could inhibit the activity of the selected enzymes.
Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (∆Gbind) value of -8.30 kcal mol-1, comparable to OTV with ∆Gbind of -8.72 kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50 ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.
Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anti-cancer drugs due to the lack of tumour-targeting activity in conventional pharmaceuticals. Poly(caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles have attracted significant attention as a potential drug carrier intended for human use. Since their first discovery, the Food and Drug Administration (FDA)-approved polymers have been studied extensively for various biomedical applications, specifically cancer therapy. The application of PCL-PEG micelles in different cancer therapies has been recorded in countless research studies for their efficacy as drug cargos. However, systematic studies on the effectiveness of PCL-PEG micelles of specific cancers for pharmaceutical applications are still lacking. As breast cancer is reported as the most prevalent cancer worldwide, we aim to systematically review all available literature that has published research findings on the PCL-PEG-based micelles as drug cargo for therapy. We further discussed the preparation method and the anti-tumour efficacy of the micelles. Using a prearranged search string, Scopus and Science Direct were selected as the databases for the systematic searching strategy. Only eight of the 314 articles met the inclusion requirements and were used for data synthesis. From the review, all studies reported the efficiency of PCL-PEG-based micelles, which act as drug cargo for breast cancer therapy.
Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS elemental analysis, and proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The vibrational frequencies of 4-PT were studied theoretically using vibrational energy distribution analysis (VEDA). Density functional theory (DFT) was applied to elucidate its chemical properties, including the Mulliken atomic charges, molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM) and reduced density gradient non-covalent interactions (RDG-NCIs). Moreover, 4-PT was compared with kojic acid in terms of its effectiveness as a tyrosinase inhibitor and anti-browning agent. The toxicity and physicochemical properties of 4-PT were predicted via ADME evaluation, which proved that 4-PT is safer than kojic acid. Experimentally, 4-PT (IC50 = 5.82 μM, browning index (10 days) = 0.292 ± 0.002) was proven to be an effective tyrosinase inhibitor and anti-browning agent compared to kojic acid (IC50 = 128.17 μM, browning index (10 days) = 0.332 ± 0.002). Furthermore, kinetic analyses indicated that the type of tyrosinase inhibition is a mixed inhibition, with Km and Vmax values of 0.85 mM and 2.78 E-09 μM/s, respectively. Finally, the mechanism of 4-PT for tyrosinase inhibition was proven by 1D, second derivative and 2D IR spectroscopy, molecular docking and molecular dynamic simulation approaches.
A new series of N-sec/tert-butyl 2-arylbenzimidazole derivatives was synthesised in 85-96% yields within 2-3.5 min by condensing ethyl 3-amino-4-butylamino benzoate with various substituted metabisulfite adducts of benzaldehyde under focused microwave irradiation. The benzimidazole analogues were characterised using (1)H NMR, (13)C NMR, high resolution MS and melting points. Evaluation of antiproliferative activity of the benzimidazole analogues against MCF-7 and MDA-MB-231 revealed several compounds with unexpected selective inhibitions of MDA-MB-231 in micromolar range. All analogues were found inactive towards MCF-7. The most potent inhibition against MDA-MB-231 human breast cancer cell line came from the unsubstituted 2-phenylbenzimidazole 10a.
A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.
Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.