An unexpected synthesis of 3,5-diaryl-1,2,4-thiadiazoles from thiobenzamides and methyl bromocyanoacetate

Aryl thioamides undergo very rapid condensation in the presence of methyl bromocyanoacetate to provide quantitative yields of 3,5-diaryl-1,2,4-thiadiazoles with an easy work-up and a high degree of product purity. The method can be scaled up with no loss in efficiency.     

Instantaneous photocatalytic degradation of malachite green dye under visible light using novel green Co–ZnO/algae composites

Research on Chemical Intermediates - Nano-ZnO and Co–ZnO supported algae (Sargassum species) were synthesized as a novel composite of promising photocatalytic activities in decolorization of...     

Development and Validation of Different Spectrophotometric and High-Performance Thin-Layer Chromatographic Methods for the Determination of Fosinopril Sodium,Hydrochlorothiazide, and Chlorothiazide as Hydrochlorothiazide Impurity

JPC – Journal of Planar Chromatography – Modern TLC - Three simple, sensitive, and validated methods were developed for the quantitative determination of fosinopril sodium (FOS) and...     

Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions.     

Synthesis of New Hybrid Structured Magnetite Crosslinked Poly Ionic Liquid for Efficient Removal of Coomassie Brilliant Blue R-250 Dye in Aqueous Medium

In this work, new crosslinked pyridinium poly ionic liquid and its magnetite hybrid structured composite were prepared and applied to remove the toxic dye Coomassie Brilliant Blue (CBB-R250) from aqueous solutions. In this respect, vinyl pyridine, maleic anhydride, and dibromo nonane were used to prepare crosslinked quaternized vinyl pyridinium/maleic anhydride ionic liquid (CQVP-MA). Furthermore, a linear copolymer was prepared by the reaction of vinyl pyridine with bromo nonane followed by its copolymerization with maleic anhydride in order to use it as a capping agent for magnetite nanoparticles. The monodisperse MNPs were incorporated into the crosslinked PIL (CQVP-MA) by ultrasonication to prepare CQVP-MA/Fe₃O₄ composite to facilitate its recovery using an external magnetic field and enhance its adsorption capacity. The chemical structures, thermal stabilities, zeta potential, particle size, EDS, and SEM of the prepared CQVP-MA and CQVP-MA/Fe₃O₄ were investigated. Adsorption kinetics, isotherms, and mechanisms of CB-R250 elimination from aqueous solutions using CQVP-MA and CQVP-MA/Fe₃O₄ were also studied, and the results revealed that the pseudo second-order kinetic model and the Langmuir isotherm model were the most suitable to describe the CBB adsorption from an aqueous solution. The adsorption capacities of CQVP-MA and CQVP-MA/Fe₃O₄ were found to be 1040 and 1198, respectively, which are more than those for previously reported material in the literature with reasonable stability for five cycles.     

Novel Thiadiazole-Based Molecules as Promising Inhibitors of Black Fungi and Pathogenic Bacteria: In Vitro Antimicrobial Evaluation and Molecular Docking Studies

Novel 1,3,4-thiadiazole derivatives were synthesized through the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate and the appropriate hydrazonoyl halides in the presence of a few drops of diisopropylethylamine. The chemical structure of the newly fabricated compounds was inferred from their microanalytical and spectral data. With the increase in microbial diseases, fungi remain a devastating threat to human health because of the resistance of microorganisms to antifungal drugs. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) have higher mortality rates in many populations. The present study aimed to find new antifungal agents using the disc diffusion method, and minimal inhibitory concentration (MIC) values were estimated by the microdilution assay. An in vitro experiment of six synthesized chemical compounds exhibited antifungal activity against Rhizopus oryzae; compounds with an imidazole moiety, such as the compound 7, were documented to have energetic antibacterial, antifungal properties. As a result of these findings, this research suggests that the synthesized compounds could be an excellent choice for controlling black fungus diseases. Furthermore, a molecular docking study was achieved on the synthesized compounds, of which compounds 2, 6, and 7 showed the best interactions with the selected protein targets.     

Exploring Natural Product Activity and Species Source Candidates for Hunting ABCB1 Transporter Inhibitors: An In Silico Drug Discovery Study

The P-glycoprotein (P-gp/ABCB1) is responsible for a xenobiotic efflux pump that shackles intracellular drug accumulation. Additionally, it is included in the dud of considerable antiviral and anticancer chemotherapies because of the multidrug resistance (MDR) phenomenon. In the search for prospective anticancer drugs that inhibit the ABCB1 transporter, the Natural Product Activity and Species Source (NPASS) database, containing >35,000 molecules, was explored for identifying ABCB1 inhibitors. The performance of AutoDock4.2.6 software to anticipate ABCB1 docking score and pose was first assessed according to available experimental data. The docking scores of the NPASS molecules were predicted against the ABCB1 transporter. Molecular dynamics (MD) simulations were conducted for molecules with docking scores lower than taxol, a reference inhibitor, pursued by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. On the basis of MM-GBSA calculations, five compounds revealed promising binding affinities as ABCB1 inhibitors with ΔG_binding < −105.0 kcal/mol. The binding affinity and stability of the identified inhibitors were compared to the chemotherapeutic agent. Structural and energetical analyses unveiled great steadiness of the investigated inhibitors within the ABCB1 active site throughout 100 ns MD simulations. Conclusively, these findings point out that NPC104372, NPC475164, NPC2313, NPC197736, and NPC477344 hold guarantees as potential ABCB1 drug candidates and warrant further in vitro/in vivo tests.     

Metabolomic Profiling and Molecular Networking of Nudibranch-Associated Streptomyces sp. SCSIO 001680

Antibiotic-resistant bacteria are the primary source of one of the growing public health problems that requires global attention, indicating an urgent need for new antibiotics. Marine ecosystems are characterized by high biodiversity and are considered one of the essential sources of bioactive chemical compounds. Bacterial associates of marine invertebrates are commonly a source of active medicinal and natural products and are important sources for drug discovery. Hence, marine invertebrate-associated microbiomes are a fruitful resource for excavating novel genes and bioactive compounds. In a previous study, we isolated Streptomyces sp. SCSIO 001680, coded as strain 63, from the Red Sea nudibranch Chromodoris quadricolor, which exhibited antimicrobial and antitumor activity. In addition, this isolate harbors several natural product biosynthetic gene clusters, suggesting it has the potential to produce bioactive natural products. The present study aimed to investigate the metabolic profile of the isolated Streptomyces sp. SCSIO 001680 (strain 63) and to predict their potential role in the host’s survival. The crude metabolic extracts of strain 63 cultivated in two different media were characterized by ultra-high-performance liquid chromatography and high-resolution mass spectrometry. The metabolomics approach provided us with characteristic chemical fingerprints of the cellular processes and the relative abundance of specific compounds. The Global Products Social Molecular Networking database was used to identify the metabolites. While 434 metabolites were detected in the extracts, only a few compounds were identified based on the standards and the public spectral libraries, including desferrioxamines, marineosin A, and bisucaberin, halichoblelide, alternarin A, pachastrelloside A, streptodepsipeptide P1 1B, didemnaketal F, and alexandrolide. This finding suggests that this strain harbors several novel compounds. In addition, the metabolism of the microbiome of marine invertebrates remains poorly represented. Thus, our data constitute a valuable complement to the study of metabolism in the host microbiome.     

Spectrofluorimetric Approach for Quantification of Cyclizine in the Presence of its Toxic Impurities in Human Plasma; in silico Study and ADMET Calculations

Journal of Fluorescence - Cyclizine (CYZ); an antiemetic compound; is widely misused for its euphoric or hallucinatory effects, either by oral or intravenous routes. The concomitant abuse of CYZ...     

1,3-Dipolar cycloaddition of vinyloxy quinolines with α-alkoxy carbonyl aldonitrones or cyclic surrogates: A comparative study for an asymmetric access to trans 4-quinolinoxy oxaprolines

The asymmetric access to unreported trans 4-quinolinoxy oxaproline precursors is investigated here in a comparative way by 1,3-dipolar cycloaddition of vinyloxy quinolines with chiral α-alkoxycarbonyl aldonitrones and chiral cyclic surrogates.