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Aza-heterocyclic scaffolds are privileged cores in the composition of their potential therapeutic profiles and versatile synthetic intermediates. Pyrazole is one of the frequently studied compounds of "azole" family and consists of nitrogen in a 1,2 linking sequence. These motifs possess a wide-spectrum of applications in the field of pharmaceuticals, agrochemicals, polymer chemistry, cosmetics, food industries and more. In addition, functionalized pyrazole derivatives are frequently used as ligands in coordination chemistry and metal-catalysed reactions. As exemplified by numerous recent reports, pyrazoles are highly promising pharmacophores with excellent therapeutic applications. Owing to their aromaticity, the ring structures have many reactive positions, where electrophilic, nucleophilic, alkylation and oxidative reactions might occur. The structural adroitness and diversity of pyrazole cores further emanated numerous fused bicyclic skeletons with various biological applications. In this review, we highlight the recent synthetic methods developed for the preparation of functionalized pyrazole derivatives (From 2017 to present). In addition, we have also covered the notable biological activities (anti-cancer, anti-inflammatory, anti-bacterial and anti-viral) of this ubiquitous core. Herein, we emphasised the synthesis of pyrazoles from variety of precursors such as, alkynes, α,β-unsaturated carbonyl compounds, diazo reagents, nitrile imines, diazonium salts, 1,3-dicarbonyl compounds and etc. Moreover, the recent synthetic methodologies focusing on the preparation of pyrazolines and pyrazolones and variously fused-pyrazoles are also included. Authors expect this review could significantly help the researchers in finding elegant novel tools to synthesize pyrazole skeletons and expand their biological evaluation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Herein, we describe the first consistent regiospecific reaction of isothiocyanates with a variety of substituted N -arylcyanothioformamides in a 1:1 molar ratio to generate a series of imidazolidineiminodithiones decorated with a multitude of functional groups on both aromatic rings. The reaction is carried out at room temperature using a 20 mol% catalytic amount of triethylamine with DMF as the solvent to selectively form the mentioned products with exclusive regioselectivity. The methodology features wide substrate scope, no requirement for chromatography, and good to high reaction yields. The products were isolated by simple ether/brine extraction and the structures were verified by multinuclear NMR spectroscopy and high accuracy mass measurements. The first conclusive molecular structure elucidation of the observed regioisomer was established by single-crystal X-ray diffraction analysis. Likewise, the tautomer of the N -arylcyanothioformamide reactant was proven by X-ray diffraction analysis. Density functional theory computations at the B3LYP-D4/def2-TZVP level in implicit DMF solvent were conducted to support the noted regiochemical outcome and proposed mechanism.

Integrin αIIbβ3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryo-EM structures of the full-length αIIbβ3, which covers three distinct states along the activation pathway. Firstly, we obtain the αIIbβ3 structure at 3 Å resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn 2+ agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show conformational changes of the αIIbβ3 activating trajectory and a unique twisting of the integrin legs, which is required for platelets accumulation. Our structure provides direct structural evidence for how the lower legs are involved in full-length integrin activation mechanisms and offers a new strategy to target the αIIbβ3 lower leg., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Terpyridine-based metal complexes have emerged as versatile and indispensable building blocks in the realm of modern chemistry, offering a plethora of applications spanning from materials science to catalysis and beyond. This comprehensive review article delves into the multifaceted world of terpyridine complexes, presenting an overview of their synthesis, structural diversity, and coordination chemistry principles. Focusing on their diverse functionalities, we explore their pivotal roles in catalysis, supramolecular chemistry, luminescent materials, and nanoscience. Furthermore, we highlight the burgeoning applications of terpyridine complexes in sustainable energy technologies, biomimetic systems, and medicinal chemistry, underscoring their remarkable adaptability to address pressing challenges in these fields. By elucidating the pivotal role of terpyridine complexes as versatile building blocks, this review provides valuable insights into their current state-of-the-art applications and future potential, thus inspiring continued innovation and exploration in this exciting area of research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An unprecedented and efficient three-component 1,3-dipolar cycloaddition reaction using ( E)- 2-(benzo[d]thiazol-2-yl)-3-(aryl)acrylonitriles 4a - g and an in situ generated azomethine ylide 3 from isatin and N -methylglycine is described. The reaction exhibits exclusive regioselectivity, resulting in the formation of 3'-(benzo[ d ]thiazol-2-yl)-1'-methyl-2-oxo-4'-(aryl)spiro[indoline-3,2'-pyrrolidine]-3'-carbonitriles regioisomers through exo / endo approaches. The diastereoselectivity of the reaction is highly dependent on the substitution pattern of the phenyl ring in dipolarophiles 4a - g , leading to the formation of exo- / endo -cycloadducts in varying ratios. To understand the stereoselectivity, the transition state structures were optimized using the TS guess geometry with the QST3-based method. The reaction mechanism and regioselectivity were elucidated by evaluating global and local electrophilicity and nucleophilicity descriptors at the B3LYP/cc-pVTZ level of theory, along with considerations based on the HSAB principle. The analysis of global electron density transfer (GEDT) showed that the reactions are polar and electron density fluxes from azomethine ylide 3 toward dipolarophile 4a - g . It was found from the molecular electrostatic potential map (MESP) that at the more favorable transition state, approach of reactants locates the oppositely charged regions over each other resulting in attractive forces between the two fragments. The computational results are consistent with the experimental observations, confirming that the reactions proceed through an asynchronous one-step mechanism., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Imidazopyridazines are fused heterocycles, like purines, with a pyridazine ring replacing the pyrimidine ring in purines. Imidazopyridazines have been primarily studied for their kinase inhibition activity in the development of new anticancer and antimalarial agents. In addition to this, they have also been investigated for their anticonvulsant, antiallergic, antihistamine, antiviral, and antitubercular properties. Herein, we review the background and development of different imidazopyridazines as potential pharmacological agents. Moreover, the scope of this relatively less charted heterocyclic scaffold is also highlighted., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Even in the era of smart technologies and IoT enabled devices, tea testing technique continues to be a person specific subjective task. In this study, we have employed optical spectroscopy-based detection technique for the quantitative validation of tea quality. In this regard, we have employed the external quantum yield of quercetin at 450 nm (λ ex  = 360 nm), which is an enzymatic product generated by the activity of β-glucosidase on rutin, a naturally occurring metabolite responsible for tea-flavour (quality). We have found that a specific point in a graph representing Optical Density and external Quantum Yield as independent and dependent variables respectively of an aqueous tea extract objectively indicates a specific variety of the tea. A variety of tea samples from various geographical origin have been analysed with the developed technique and found to be useful for the tea quality assessment. The principal component analysis distinctly showed the tea samples originated from Nepal and Darjeeling having similar external quantum yield, while the tea samples from Assam region had a lower external quantum yield. Furthermore, we have employed experimental and computational biology techniques for the detection of adulteration and health benefit of the tea extracts. In order to assure the portability/field use, we have also developed a prototype which confirms the results obtained in the laboratory. We are of the opinion that the simple user interface and almost zero maintenance cost of the device will make it useful and attractive with minimally trained manpower at low resource setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The recent prediction of diabetes to be a global pandemic invites a detection strategy preferably non-invasive, and bloodless to manage the disease and the associated complications. Here, we have synthesized chitosan polymer functionalized, organic-inorganic bio-compatible nano-hybrids of Mn 3 O 4 nanoparticles, and characterized it by utilizing several optical methodologies for the structural characterization which shows the Michaelis Menten (MM) kinetics for glucose and alpha-amylase protein (well-known diabetes biomarkers). We have also studied the potentiality for the detection of alpha-amylase in human salivary secretion which is reported to be strongly correlated with uncontrolled hyperglycemia. Finally, we have developed a prototype for the measurement of glucose (LOD of 0.38 mg/dL, LOQ of 1.15 mg/dL) and HbA1c (LOD of 0.15% and LOQ of 0.45%) utilizing the basic knowledge in the study for the detection of uncontrolled hyperglycemia at the point-of-care. With the limited number of clinical trials, we have explored the potential of our work in combating the diabetic pandemic across the globe in near future., (© 2023. Springer Nature Limited.)

Isoselenocyanates are valuable coupling partners required for preparing key chemical intermediates and biologically active molecules in an accelerated and effective way. Likewise, (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been employed in numerous one-step heteroannulation reactions to assemble the structural core of several various kinds of heterocyclic compounds. Here, we describe the inverse electron demand 1,3-dipolar cycloaddition reaction of isoselenocyanates with a variety of substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to generate, regioselectively and stereoselectively, a series of 5-arylimino-1,3,4-selenadiazole derivatives comprising a multitude of functional groups on both aryl rings. The synthetic method features gentle room-temperature conditions, wide substrate scope, and good to high reaction yields. The selenadiazoles were separated by gravity filtration in all instances and chemical structures were validated by multinuclear NMR spectroscopy and high accuracy mass spectral measurements. First conclusive molecular structure elucidation of the observed 5-arylimino-selenadiazole regioisomer was verified by single-crystal X-ray diffraction analysis. Crystal-structure measurement was successfully carried out on (Z)-1-(4-(4-iodophenyl)-5-(p-tolylimino)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one and (Z)-1-(5-((4-methoxyphenyl)imino)-4-(4-(methylthio)phenyl)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one. Likewise, the (Z)-geometry of the hydrazonoyl chloride reactant was proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (Z)-2-oxo-N-phenylpropanehydrazonoyl chloride and (Z)-N-(3,5-bis(trifluoromethyl)phenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were conducted to support the noted experimental findings and suggested mechanism., (© 2023 Wiley-VCH GmbH.)

Recent findings suggest a key role for reactive oxygen species (ROS) in the pathogenesis and progression of ulcerative colitis (UC). Several studies have also highlighted the efficacy of citrate functionalized Mn 3 O 4 nanoparticles as redox medicine against a number of ROS-mediated disorders. Here we show that synthesized nanoparticles consisting of chitosan functionalized tri-manganese tetroxide (Mn 3 O 4 ) can restore redox balance in a mouse model of UC induced by dextran sulfate sodium (DSS). Our in-vitro characterization of the developed nanoparticle confirms critical electronic transitions in the nanoparticle to be important for the redox buffering activity in the animal model. A careful administration of the developed nanoparticle not only reduces inflammatory markers in the animals, but also reduces the mortality rate from the induced disease. This study provides a proof of concept for the use of nanomaterial with synergistic anti-inflammatory and redox buffering capacity to prevent and treat ulcerative colitis., (© 2023. The Author(s).)

Benzothiazepines are pharmacologically active compounds, frequently utilized as a precursor for acquiring versatile molecules with several bioactivities including anti-inflammatory, anti-human immunodeficiency virus (anti-HIV), analgesic, antitumor, antimicrobial, and antitubercular. In this study, the 2,4-diphenyl-2,3-dihydro-1,5-benzothiazepine scaffold was selected for their in vitro , docking, and druglikeness studies to evaluate their inhibitory potential against mushroom tyrosinase. All synthesized analogues, 1 - 14 , exhibited moderate to good IC 50 values ranging from 1.21 to 70.65 μM. The synthesized benzothiazepine derivatives were potent tyrosinase inhibitors, which outperformed the reference kojic acid (IC 50 = 16.69 μM). The kinetic analysis revealed that compound 2 (2-(3,4-dimethoxyphenyl)-4-( p -tolyl)-2,3-dihydrobenzo[ b ][1,4]thiazepine) was a mixed-type tyrosinase inhibitor with a K i value of 1.01 μM. Molecular modeling studies against tyrosinase protein (PDB ID: 2Y9X) were conducted to recognize the binding modes of these analogues. The utilization of molecular dynamic (MD) simulations enabled the assessment of the protein-ligand complex's dynamic behavior, stability, and binding affinity for the compounds. These simulations ultimately led to the identification of compound 2 as a potential inhibitor of tyrosinase. Additionally, a druglikeness study was conducted, which supported the promising potential of the new analogues as novel antityrosinase agents. The in silico studies were consistent with the in vitro results, showing that these ligands had good binding scores against tyrosinase and interacted with the core residues of the target protein. Gaussian 09 was used for the geometry optimization of all complexes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In comparison to physicochemical and chemical methods, microbial dye biosorption is regarded as an eco-effective and economically viable alternative and is a widely applied method due to its high efficiency and compatibility with the environment. Therefore, the idea of this study is to clarify to what extent the viable cells and the dry biomass of Pseudomonas alcaliphila NEWG-2 can improve the biosorption of methylene blue (MB) from a synthetic wastewater sample. The array of Taguchi paradigm has been conducted to ascertain five variables affecting the biosorption of MB by broth forms of P. alcaliphila NEWG. The data of MB biosorption were familiar to the predicted ones, indicating the precision of the Taguchi model's prediction. The maximum biosorption of MB (87.14%) was achieved at pH 8, after 60 h, in a medium containing 15 mg/ml MB, 2.5% glucose, and 2% peptone, with sorting the highest signal-to-noise ratio (38.80). FTIR spectra detected various functional groups (primary alcohol, α, β-unsaturated ester, symmetric NH 2 bending, and strong C-O stretching) on the bacterial cell wall that participated in the biosorption of MB. Furthermore, the spectacular MB biosorption ability was validated by equilibrium isotherms and kinetic studies (the dry biomass form), which were derived from the Langmuir model (q max  = 68.827 mg/g). The equilibrium time was achieved in about 60 min, with 70.5% of MB removal. The biosorption kinetic profile might be adequately represented by pseudo-second order and Elovich models. The changes in the bacterial cells before and after the biosorption of MB were characterized using a scanning electron microscope. As realized from the aforementioned data, the bacterium is a talented, effective, eco-friendly, and low-cost bio-sorbent for the decolorization and remedy of an industrial effluent containing MB from an aqueous environment. The current outcomes in the biosorption of MB molecules promote the use of the bacterial strain as viable cells and/or dry biomass in ecosystem restoration, environmental cleanup, and bioremediation studies., (© 2023. The Author(s).)

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N -alkyl-1 H -indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC 50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

N -arylcyanothioformamides are useful coupling components for building key chemical intermediates and biologically active molecules in an expedited and efficient manner. Similarly, substituted ( Z )-2-oxo- N -phenylpropanehydrazonoyl chlorides have been utilized in numerous one-step heteroannulation reactions to assemble the structural core of several different types of heterocyclic compounds. Herein, we demonstrate the effectiveness of the reaction of N -arylcyanothioformamides with various substituted ( Z )-2-oxo- N -phenylpropanehydrazonoyl chlorides to produce, stereoselectively and regioselectively, a range of 5-arylimino-1,3,4-thiadiazole derivatives decorated with a multitude of functional groups on both aromatic rings. The synthetic methodology features mild room-temperature conditions, large substrate scope, wide array of functional groups on both reactants, and good to high reaction yields. The products were isolated by gravity filtration in all cases and structures were confirmed by multinuclear NMR spectroscopy and high accuracy mass spectral analysis. Proof of molecular structure of the isolated 5-arylimino-1,3,4-thiadiazole regioisomer was obtained for the first time by single-crystal X-ray diffraction analysis. Crystal-structure determination was carried out on ( Z )-1-(5-((3-fluorophenyl)imino)-4-(4-iodophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one and ( Z )-1-(4-phenyl-5-( p -tolylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one. Similarly, the tautomeric structures of the N -arylcyanothioformamides and ( Z )-geometries of the 2-oxo- N -phenylpropanehydrazonoyl chloride coupling partners were proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (4-ethoxyphenyl)carbamothioyl cyanide and (Z)-N -(2,3-difluorophenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were carried out to rationalize the observed experimental findings., Competing Interests: The authors declare no conflict of interest.

The study was aimed to evaluate the performance of a newly developed spectroscopy-based non-invasive and noncontact device (SAMIRA) for the simultaneous measurement of hemoglobin, bilirubin and oxygen saturation as an alternative to the invasive biochemical method of blood sampling. The accuracy of the device was assessed in 4318 neonates having incidences of either anemia, jaundice, or hypoxia. Transcutaneous bilirubin, hemoglobin and blood saturation values were obtained by the newly developed instrument which was corroborated with the biochemical blood tests by expert clinicians. The instrument is trained using Artificial Neural Network Analysis to increase the acceptability of the data. The artificial intelligence incorporated within the instrument determines the disease condition of the neonate. The Pearson's correlation coefficient, r was found to be 0.987 for hemoglobin estimation and 0.988 for bilirubin and blood gas saturation respectively. The bias and the limits of agreement for the measurement of all the three parameters were within the clinically acceptance limit., (© 2023. The Author(s).)

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds.

Infections caused by bacteria are a significant issue on a global scale, and imperative action is required to discover novel or improved therapeutic agents. Flavonoids are a class of plant-derived compounds that have a variety of potentially useful bioactivities. These activities include immediate antimicrobial properties, synergistic effect with antimicrobials, ferocious repression of pathogenicity, anti-urease activity etc. This review summarizes current studies concerning anti-urease actions of flavonoids as well as structural-activity correlation investigations of the flavonoid core structure. It is possible that if researchers investigate the many structural changes that may be made in flavonoid rings, they'll be able to build up novel compounds that have powerful and effective anti-urease properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The beneficial microorganisms represent a new and hopeful solution for a sustainable environment and development. In this investigation, Trichoderma asperellum ZNW, isolated from seeds, was domiciliated within the pea plant for improving growth, disease management, and enhancement of productivity. Globisporangium ultimum NZW was isolated from deformed pea seeds, representing the first record of the pathogen caused by pea damping-off. Both fungi were molecularly identified. T. asperellum ZNW produced several lytic enzymes and bioactive metabolites as detected by GC-MC. The SEM illustrated the mycoparasitic behavior of T. asperellum ZNW on G. ultimum NZW mycelia. In the pot experiment, T. asperellum domiciliated the root and grew as an endophytic fungus, leading to root vessel lignification. Under soil infection, T. asperellum reduced damping-off, by enhancing peroxidase, polyphenol, total phenols, and photosynthetic pigments content. The vegetative growth, yield, and soil dehydrogenase activity were improved, with an enhancement in the numerical diversity of the microbial rhizosphere. This work may enable more understanding of the plant-fungal interaction, yet, working on domiciliation is recommended as a new approach to plant protection and growth promotion under various ecological setups.

Anti-microbial resistant infection is predicted to be alarming in upcoming years. In the present study, we proposed co-localization of two model drugs viz., rifampicin and benzothiazole used in anti-tuberculosis and anti-fungal agents respectively in a nanoscopic cationic micelle (cetyl triethyl ammonium bromide) with hydrodynamic diameter of 2.69 nm. Sterilization effect of the co-localized micellar formulation against a model multi-drug resistant bacterial strain viz., Methicillin resistant Staphylococcus aureus was also investigated. 99.88% decrease of bacterial growth in terms of colony forming unit was observed using the developed formulation. While Dynamic Light Scattering and Forsters Resonance Energy Transfer between benzothiazole and rifampicin show co-localization of the drugs in the nanoscopic micellar environment, analysis of time-resolved fluorescence decays by Infelta-Tachiya model and the probability distribution of the donor-acceptor distance fluctuations for 5 μM,10 μM and 15 μM acceptor concentrations confirm efficacy of the co-localization. Energy transfer efficiency and the donor acceptor distance are found to be 46% and 20.9 Å respectively. We have also used a detailed computational biology framework to rationalize the sterilization effect of our indigenous formulation. It has to be noted that the drugs used in our studies are not being used for their conventional indication. Rather the co-localization of the drugs in the micellar environment shows a completely different indication of their use in the remediation of multi-drug resistant bacteria revealing the re-purposing of the drugs for potential use in hospital-born multi-drug resistant bacterial infection., (© 2022. The Author(s).)

The deteriorating water environment worldwide, mainly due to population explosion and uncontrolled direct disposal of harmful industrial and farming wastes, earnestly demands new approaches and accurate technologies to monitor water quality before consumption overcoming the shortcomings of the current methodologies. A spectroscopic water quality monitoring and early-warning instrument for evaluating acute water toxicity are the need of the hour. In this study, we have developed a prototype capable of the quantification of dissolved organic matter, dissolved chemicals, and suspended particulate matter in trace amounts dissolved in the water. The prototype estimates the water quality of the samples by measuring the absorbance, fluorescence, and scattering of the impurities simultaneously. The performance of the instrument was evaluated by detecting common water pollutants such as Benzopyrene, Crystal Violet, and Titanium di-oxide. The limit of detection values was found to be 0.50, 23.9, and 23.2 ppb (0.29 µM), respectively.

The present investigation has been designed by Taguchi and hybrid artificial neural network (ANN) paradigms to improve and optimize the binary sorption of Cobalt(II) and methylene blue (MB) from an aqueous solution, depending on modifying physicochemical conditions to generate an appropriate constitution for a highly efficient biosorption by the alga; Sargassum latifolium. Concerning Taguchi's design, the predicted values of the two responses were comparable to actual ones. The biosorption of Cobalt(II) ions was more efficient than MB, the supreme biosorption of Cobalt(II) was verified in run L 21 (93.28%), with the highest S/N ratio being 39.40. The highest biosorption of MB was reached in run L 22 (74.04%), with a S/N ratio of 37.39. The R 2 and adjusted R 2 were in reasonable values, indicating the validity of the model. The hybrid ANN model has exclusively emerged herein to optimize the biosorption of both Cobalt(II) and MB simultaneously, therefore, the ANN model was better than the Taguchi design. The predicted values of Cobalt(II) and MB biosorption were more obedience to the ANN model. The SEM analysis of the surface of S. latifolium showed mosaic form with massive particles, as crosslinking of biomolecules of the algal surface in the presence of Cobalt(II) and MB. Viewing FTIR analysis showed active groups e.g., hydroxyl, α, β-unsaturated ester, α, β-unsaturated ketone, N-O, and aromatic amine. To the best of our knowledge, there are no reports deeming the binary sorption of Cobalt(II) and MB ions by S. latifolium during Taguchi orthogonal arrays and hybrid ANN., (© 2022. The Author(s).)

Selenoureas are widespread as useful elements for constructing important species and biologically active molecules. Finding an efficient and straightforward method to prepare this motif and biologically screen derivatives thereof is crucial. Herein, we demonstrate the effectiveness of using ethanol as a solvent in the preparation of various substituted aryl-, benzyl-, and piperazine-selenoureas from isoselenocyanates and amines. The synthetic method includes mild reaction conditions, large substrate scope, and good isolated yields. Biological evaluation of the prepared products on MDA-MB-231 and MCF-7 cancer cell lines revealed several remarkably active compounds (IC 50 < 10 μΜ) with the best one exhibiting IC 50 values of 1.8 μΜ and 1.2 μΜ observed against the challenging former triple-negative breast cancer cell line and the latter one, respectively. The chemical structures of all new compounds were fully characterized by multinuclear nuclear magnetic resonance (NMR) spectroscopy and high accuracy mass measurements., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Prodigiosin is a secondary metabolite produced in several species of bacteria. It exhibits antimicrobial and anticancer properties. Methods for the extraction and identification of prodigiosin and their related derivatives from bacterial cultures typically depend on solvent-based extractions followed by NMR spectroscopy. The estuarine bacterium, V. gazogenes PB1, was previously shown to produce prodigiosin. This conclusion, however, was based on analytical data obtained from ultraviolet-visible absorption spectrophotometry and infrared spectroscopy. Complete dependence on these techniques would be considered inadequate for the accurate identification of the various members of the prodiginine family of compounds, which possess very similar chemical structures and near-identical optical properties. In this study, we extracted prodigiosin from a culture of Vibrio gazogenes PB1 cultivated in minimal media, and for the first time, confirmed the synthesis of prodigiosin Vibrio gazogenes PB1 using NMR techniques. The chemical structure was validated by 1 H and 13 C NMR spectroscopy, and further corroborated by 2D NMR, which included 1 H- 1 H-gDQFCOSY, 1 H- 13 C-gHSQC, and 1 H- 13 C-gHMBC, as well as 1 H- 1 H-homonuclear decoupling experiments. Based on this data, previous NMR spectral assignments of prodigiosin are reaffirmed and in some cases, corrected. The findings will be particularly relevant for experimental work relating to the use of V. gazogenes PB1 as a host for the synthesis of prodigiosin.

Ralstonia solanacearum is one of the globally significant plant pathogens that infect a wide host range of economically important plants. A study was conducted to evaluate the hypothesis that an avirulent strain of R. solanacearum can act as a biocontrol mediator for managing potato bacterial wilt. Virulent R. solanacearum was isolated and identified (GenBank accession number; OP180100). The avirulent strain was obtained from the virulent strain through storage for 3 weeks until the development of deep red colonies. The virulent strain had higher lytic activity than the avirulent strain. Tubers' treatments by the avirulent strain of R. solanacearum , (supernatant, boiled supernatant, and dead cells) significantly reduced plant disease rating and increased the growth, physiological activities, and biomass of potato compared to the untreated, infected control. The major components detected by GC-MS in the supernatant revealed 10.86% palmitic acid (virulent), and 18.03% 1,3-dioxolane, 2,4,5-trimethyl- (avirulent), whereas the major component in the boiled supernatant was 2-hydroxy-gamma-butyrolactone in the virulent (21.17%) and avirulent (27.78%) strains. This is the first research that assessed the influence of boiled supernatant and dead cells of virulent and avirulent R. solanacearum strains in controlling bacterial wilt disease. Additional work is encouraged for further elucidation of such a topic., Competing Interests: The authors declare no conflict of interest.

Enzyme function can be altered via modification of its amino acid residues, side chains and large-scale domain modifications. Herein, we have addressed the role of residue modification in catalytic activity and molecular recognition of an enzyme alpha-chymotrypsin (CHT) in presence of a covalent cross-linker formalin. Enzyme assay reveals reduced catalytic activity upon increased formalin concentration. Polarization gated anisotropy studies of a fluorophore 8-Anilino-1-naphthalenesulfonic acid (ANS) in CHT show a dip rise pattern in presence of formalin which is consistent with the generation of multiple ANS binding sites in the enzyme owing to modifications of its local amino acid residues. Molecular docking study on amino acid residue modifications in CHT also indicate towards the formation of multiple ANS binding site. The docking model also predicted no change in binding behavior for the substrate Ala-Ala-Phe-7-amido-4-methylcoumarin (AMC) at the active site upon formalin induced amino acid cross-linking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biswas, Adhikari, Pal, Mondal, Mukherjee, Ghosh, Obaid, Moussa, Choudhury, Ahmed, Das and Pal.)

The usual treatment for anemia and especially for anemia of inflammation (also called anemia of chronic disease) is supportive care with the target of improving the lifestyle of the patients. There is no effective medication to date for proper management. As the inflammation, erythropoiesis, and oxidative stress are the major concerns in this case, it inspired us to use a nano-erythropoietin stimulating agent (nano-ESA) made up of a nano-complex of manganese and citrate (Mn-citrate nano-complex), which has been hypothesized to have excellent antioxidant and anti-inflammatory mechanisms. Single oral dose of the nano-ESA efficiently prevented the onset of anemia as well as led to recovery from anemia in our phenylhydrazine (PHz)-intoxicated C57BL/6J mice model of anemia without any toxicological side effects. These preliminary findings may pave the way for an affordable and safe clinical use of the nano-ESA as a rapid recovery medication of anemia, especially anemia of inflammation., Competing Interests: S.K.P., A.K.M., A.A., and P.C. have submitted a patent application (Reference Number: 202131034977) related to Mn-citrate NC and its efficacy in treatment of anemia. All other authors declare that they have no competing interests., (© 2022 The Authors.)

The objective of this study was to investigate the genetic diversity and population structure of local chicken ecotypes from Burkina Faso using microsatellite markers. A total of 71 individuals representing local chicken populations from the Centre-East (18), Centre-North (17), Sahel (18) and South-West (18) were used to estimate genetic diversity indices, population structure and phylogenetic relationships using 20 selected polymorphic microsatellite markers. The number of alleles, mean number of alleles, mean of observed and expected heterozygosity and polymorphic information content were 127, 6.35, 0.391, 0.521, 0.539 and 0.541, respectively. The estimated overall fixation index between loci (F), among populations (F IS ) and inbreeding coefficient within chicken ecotypes were 0.239, 0.267 and 0.243, respectively. Analysis of the molecular variance revealed that 77% of the total genetic diversity was attributed to within-population variation and the remaining 1% and 22% were attributed to among-regions differentiation (F ST ) and among-individual differentiation (F IT ), respectively. The highest pairwise genetic distance (0.026) was found between the local Konde ecotype and those from the Centre-North region while the lowest distance was observed between local chickens from the Sahel and the Centre-North regions (0.003). Neighbour-joining phylogenetic tree and principal component discriminant analyses confirmed the observed genetic distances between populations. The results show that local chickens in Burkina Faso have a rich genetic diversity with little differentiation between the studied populations. This study provides important information on measures of genetic diversity that could help in the design and implementation of future genetic improvement and conservation programs for local chickens in Burkina Faso.

Allosteric activation and silencing of leukocyte β2-integrins transpire through cation-dependent structural changes, which mediate integrin biosynthesis and recycling, and are essential to designing leukocyte-specific drugs. Stepwise addition of Mg 2+ reveals two mutually coupled events for the αXβ2 ligand-binding domain-the αX I-domain-corresponding to allostery establishment and affinity maturation. Electrostatic alterations in the Mg 2+ -binding site establish long-range couplings, leading to both pH- and Mg 2+ -occupancy-dependent biphasic stability change in the αX I-domain fold. The ligand-binding sensorgrams show composite affinity events for the αX I-domain accounting for the multiplicity of the αX I-domain conformational states existing in the solution. On cell surfaces, increasing Mg 2+ concentration enhanced adhesiveness of αXβ2. This work highlights how intrinsically flexible pH- and cation-sensitive architecture endows a unique dynamic continuum to the αI-domain structure on the intact integrin, thereby revealing the importance of allostery establishment and affinity maturation in both extracellular and intracellular integrin events., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

A one-step, three-component reaction between α-hydroxyketones, oxoacetonitriles, and primary amines gives N -substituted 2,3,5-functionalized 3-cyanopyrroles with complete selectivity in up to 90% isolated yields. The reaction worked on a wide substrate scope under mild reaction conditions (AcOH as a catalyst, EtOH, 70 °C, 3 h). The reaction proceeded with very high atom efficiency as water is the only molecule lost during the reaction. The practicality of the reaction was demonstrated on a large gram scale. The structures of the 3-cyanopyrroles were confirmed by single-crystal X-ray diffraction and NMR; this work provides a general and practical entry to pyrrole scaffolds suitably decorated for the synthesis of various bioactive pyrroles in a concise manner.

Heterocycles are the key structures in organic chemistry owing to their immense applications in the biological, chemical, and pharmaceutical fields. Heterocyclic compounds perform various noteworthy functions in nature, medication, innovation etc. Most frequently, pure nitrogen heterocycles or various positional combinations of nitrogen, oxygen, and sulfur atoms in five or six-membered rings can be found. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a popular strategy for the management of numerous mental diseases. In this context, cholinesterase inhibitors are utilized to relieve the symptoms of neurological illnesses like dementia and Alzheimer's disease (AD). The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD. Moreover, a detailed structure-activity relationship (SAR) has been established for the future discovery of novel drugs for the treatment of AD. Most of the heterocyclic motifs have been used in the design of new potent cholinesterase inhibitors. In this regard, this review is an endeavor to summarize the biological and chemical studies over the past decade (2010-2022) describing the pursuit of new N, O and S containing heterocycles which can offer a rich supply of promising AChE and BChE inhibitory activities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The definitive screening design (DSD) and artificial neural network (ANN) were conducted for modeling the biosorption of Co(II) by Pseudomonas alcaliphila NEWG-2. Factors such as peptone, incubation time, pH, glycerol, glucose, K 2 HPO 4 , and initial cobalt had a significant effect on the biosorption process. MgSO 4 was the only insignificant factor. The DSD model was invalid and could not forecast the prediction of Co(II) removal, owing to the significant lack-of-fit ( P < 0.0001). Decisively, the prediction ability of ANN was accurate with a prominent response for training (R 2 = 0.9779) and validation (R 2 = 0.9773) and lower errors. Applying the optimal levels of the tested variables obtained by the ANN model led to 96.32 ± 2.1% of cobalt bioremoval. During the biosorption process, Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy, and scanning electron microscopy confirmed the sorption of Co(II) ions by P. alcaliphila . FTIR indicated the appearance of a new stretching vibration band formed with Co(II) ions at wavenumbers of 562, 530, and 531 cm -1 . The symmetric amino (NH 2 ) binding was also formed due to Co(II) sorption. Interestingly, throughout the revision of publications so far, no attempt has been conducted to optimize the biosorption of Co(II) by P. alcaliphila via DSD or ANN paradigm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsayed, Moussa, Alrdahe, Alharbi, Ghoniem, El-khateeb and Saber.)

Developing a sustainable photocatalyst is crucial to mitigate the foreseeable energy shortage and environmental pollution caused by the rapid advancement of global industry. We developed Dy 2 O 3 /TiO 2 nanoflower (TNF) with a hierarchical nanoflower structure and a near-ideal anatase crystallite morphology to degrade aqueous rhodamine B solution under simulated solar light irradiation. The prepared photocatalyst was well-characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, energy-dispersive spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, diffuse reflectance UV-vis spectra, and X-ray photoelectron spectroscopy. Further analysis was performed to highlight the photoelectrochemical activity of the prepared photocatalysts such as electrochemical impedance spectroscopy, linear sweep voltammetry, photocurrent response, and a Mott-Schottky study. The crystalline Dy 2 O 3 /TNF exhibits superb photocatalytic activity attributed to the improved charge transfer, reduced recombination rate of the electron-hole pairs, and a remarkable red-shift in light absorption., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Plant residuals comprise the natural habitat of the plant pathogen; therefore, attention is currently focusing on biological-based bioprocessing of biomass residuals into benefit substances. The current study focused on the biodegradation of peanut plant residual (PNR) into citric acid (CA) through a mathematical modeling strategy. Novel endophytic Trichoderma longibrachiatum WKA55 (GenBank accession number: MZ014020.1), having lytic (cellulase, protease, and polygalacturonase) activity, and tricalcium phosphate (TCP) solubilization ability were isolated from peanut seeds and used during the fermentation process. As reported by HPLC, the maximum CA (5505.1 μg/g PNR) was obtained after 9 days in the presence of 15.49 mg TCP, and 15.68 mg glucose. GC-MS analysis showed other bioactive metabolites in the filtrate of the fermented PNR. Practically, the crude product (40%) fully inhibited (100%) the growth and spore germination of three mycotoxinogenic fungi. On peanuts, it improved the seed germination (91%), seedling features, and vigor index (70.45%) with a reduction of abnormal seedlings (9.33%). The current study presents the fundamentals for large-scale production in the industry for the sustainable development of PNR biomass as a natural source of bioactive metabolites, and safe consumption of lignocellulosic-proteinaceous biomass, as well. T. longibrachiatum WKA55 was also introduced as a novel CA producer specified on PNR. Application of the resulting metabolite is encouraged on a large scale., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Askar, Rashad, Moussa, Ghoneem, Mostafa, Al-Otibi, Arishi and Saber.)

Cyanoformamides are ubiquitous as useful components for assembling key intermediates and bioactive molecules. The development of an efficient and simple approach to this motif is a challenge. Herein, we demonstrate the effectiveness of the I 2 -DMSO oxidative system in the preparation of N -arylcyanoformamides from N -arylcyanothioformamides. The synthetic method features mild conditions, broad substrate scope, and high reaction efficiency. Furthermore, this method provides an excellent entry to exclusively afford 2-cyanobenzothiazoles which are useful substrates to access new luciferin analogs. The structures of all new products were elucidated by multinuclear NMR spectroscopy and high accuracy mass spectral analysis. Crystal-structure determination by means of single-crystal X-ray diffraction was carried out on (4-bromophenyl)carbamoyl cyanide, 5,6-dimethoxybenzo[ d ]thiazole-2-carbonitrile, 5-(benzyloxy)benzo[ d ]oxazole-2-carbonitrile, 4,7-dimethoxybenzo[ d ]thiazole-2-carbonitrile, and (5-iodo-2,4-dimethoxyphenyl)carbamoyl cyanide, a key intermediate with mechanistic implications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An efficient atom-economical synthetic protocol to access new imidazole-based N -phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC 50 values between 7.5 and 11.1 μM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors ZM., (Copyright © 2022 Malik, Alsantali, Jamal, Seddigi, Morad, Alsharif, Hussein, Jassas, Al-Rooqi, Abduljaleel, Babalgith, Altass, Moussa and Ahmed.)