Recently, it has been seen that there is a rapid surge in Click Chemistry (CC) research owing to its fast, reliable, and biocompatible nature, making it an ideal tool for drug discovery. CC approach allows facile and sustainable development of complex molecules with minimal off-target products. With the rapid advancement of the CC field, its applications have significantly expanded across various domains, including biomedical, pharmaceutical, radiochemistry, nanochemistry, polymer chemistry, and microscopy. However, its applications remain most prominent in medicinal chemistry. This review initially covers the introduction and distinct types of click reactions such as copper-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), and Diels–Alder Cycloaddition (DA), followed by the different techniques facilitating the click reactions. Among these, the CuAAC reaction is most effective and extensive CC approach widely explored for creating huge number of molecular libraries of medicinal significance due to its excellent biocompatibility, reliability, and specificity. In this review, we mainly included the synthesis and medicinal attributes of click reaction (CuAAC SPAAC)-derived organic heterocycles from 2012–2023, particularly anticancer, antiviral, antidiabetic, and antimicrobial that will help the readers to understand the concept of CC, medicinal significance of CC-derived heterocycles, unexplored areas, challenges, and future prospects. This review will also provide a roadmap for new research directions and applications of click-derived heterocycles in medicinal chemistry.

Kojic Acid (KA) is an oxygen-based heterocycle of natural occurrence and is chemically known as 5- hydroxy-2-(hydroxymethy1)-4H-pyran-4-one. This review has been designed to lighten up the various biological potentials, including the tyrosinase inhibition potential and depigmenting action of KA and its derivatives. KA has very interesting physical and chemical properties and has many applications in the medicinal and cosmetic industries, like antimicrobial, antifungal, antitumor, anti-inflammatory, and depigmentation activities. Despite its medicinal importance, KA possesses a fascinating structure with multiple reactive centers, making it valuable in various chemical transformations. Therefore, a variety of KA derivatives have been/may be prepared with improved stability and with more effective and interesting biological activities than KA itself. Here, in this review, we have briefly described the biological activities of some potent KA derivatives with a brief introduction to the physical and chemical properties of KA. This review would bridge the gap between basic research and applied science, offering value to both scientific and industrial communities.

Aurones belong to the flavonoid-based heterocyclic class of plant origin and are full of therapeutic potential. Characterized by their unique benzofuranone core structure and α,β unsaturated carbonyl group, aurones possess exceptional structural adaptability and electronic characteristics, making them excellent candidates for enzyme targeting and promising agents for drug development. Recent research has highlighted their ability to inhibit key enzymes, including cholinesterase, cathepsin B, monoamine oxidase, cyclooxygenase, and various digestive enzymes. This demonstrates their potential in treating cancer, neurodegenerative diseases, and metabolic disorders associated with the overexpression of these enzymes. The ability to functionalize the aurone scaffold further enhances its adaptability for selective and potent enzyme targeting. This review examines the structural features of aurones, their enzyme-inhibitory effects, an overview of their molecular mechanisms, and the structure-activity relationships (SAR) underlying their enzyme inhibition, supported by computational approaches. Although several review articles have addressed the synthetic and general biological profile of aurones, none have specifically focused on their enzyme inhibitory potential, which is the central theme of this review. This review offers a strong foundation and rationale for the design, synthesis, and optimization of novel aurone-based compounds aimed at achieving desirable therapeutic outcomes by targeting specific enzymes.

In the present investigation, we engineered some 1,2,3-triazole clubbed and dichloro substituted novel aurones as potential anticancer agents well capable of targeting digestive enzymes. These novel 2-(2,6-dichlorobenzylidene)-6-((1-aryl-1H-1,2,3-triazol-4-yl)methoxy)benzofuran-3(2H)-one derivatives or 1,2,3-triazoleaurone based hybrid molecules, were initially designed, synthesized, and thoroughly characterized and later studied for their impact on AGS cancer cell line and digestive enzymes. Some remarkable outcomes were observed in the anticancer screening of these compounds as almost all aurone-triazole hybrids (eighteen among ninteen) were found to exhibit IC50 values, lower (IC50= 7.73-30.69 mu M) than the reference drug leucovorin (IC50= 30.8 mu M), except for hybrid 10k (IC50= 67.03 mu M). Also in the in-vitro screening, against three digestive enzymes, most of these hybrid compounds, exhibited some significant activity. Notably, compound 10l exhibited substantial activation of lipase (% activation = 175.8 +/- 4.1), compound 10n displayed inhibition against alpha-amylase (% inhibition = 36.7 +/- 1.3), and compound 10i produced inhibition against trypsin (% inhibition = 65.7 +/- 2.0). Additionally, in-silico molecular docking was utilized to evaluate interactions between proteins and ligands, unveiling binding patterns of the novel synthesised compounds and the reference drug with the receptor proteins. Assessing therapeutic potential, an in-silico ADMET model demonstrated that the synthesized molecules possess favorable drug-like properties. The hybrids underwent computational scrutiny employing the DFT/ B3LYP method, encompassing the determination of Frontier Molecular Orbital energy values, along with the calculation of diverse quantum chemical parameters.

As part of our ongoing efforts to identify new, potentially bioactive aurones, we have designed, synthesized and evaluated a molecular library of propargyl-substituted aurones for their anticancer potential against AGS cancer cell line. We used a molecular library of thirty-nine propargylated aurones for the anticancer evaluation, including twenty new compounds (7b-7u) and nineteen additional compounds recently reported by our group (7a and 7v-7am) for another study. All the 6-propargyloxyaurones 7(a-am) displayed moderate to very good cytotoxic potential against AGS cell lines. Among all, 30 compounds were found to be more potent than the reference drug leucovorin (IC50 = 30.08 mu M). In particular, the IC50 values of 7y (Ar = 4-Br-C6H4, IC50 = 1.01 mu M) and 7al (Ar = 9-anthracenyl, IC50 = 1.02 mu M) were highly significant in comparison to the reference medication leucovorin highlighting their significant cytotoxic potential. Various spectroscopic techniques, including FT-IR, 1H and 13C-NMR, HRMS, 2D-NMR, and single crystal analysis, were used to determine the structure and configurational aspects of substituted aurone derivatives. Further, DFT, Hirshfeld surface and twodimensional fingerprint plots, molecular docking were carried out to understand the various molecular interactions and the structural aspects of these aurones.

Here in this work we successfully designed and synthesized a library of some novel pyrrolidine-triazole-aurone hybrids i.e. ( Z )-2-benzylidene-6-((1-(2-(pyrrolidin-1-yl)ethyl)-1 H -1,2,3-triazol-4-yl)methoxy)benzofuran-3(2 H )-one derivatives 5(a-k) . The structures of all the synthesized hybrid aurones were confirmed based on their spectral (FT-IR, 1 H NMR, 13 C NMR) and HRMS data. In biological studies, the impact of synthesized compounds on digestive enzymes, amylase, lipase, and trypsin was analyzed. These compounds exhibited varying effects on these enzymes as both trypsin and amylase were activated, but a significant inhibition was achieved for the lipase enzyme. Upon examining the binding energies of the synthesized compounds with the enzymes, it was observed that the experimental findings partially aligned with the docking results. These in vitro and in silico results of these hybrid aurones against digestive enzymes, signify their potential as anti-inflammatory and anti-obesity agents.

In quest of generating a diverse array of potential cytotoxic candidates through molecular hybridization approach, herein we have designed a library of forty-one morpholine-functionalized aurones 7(a-ao), each with a distinct substitution pattern. These aurones were obtained by reacting 6-hydroxyaurones, with 4-(2-chloroethyl)morpholine hydrochloride, characterized by various spectroscopic techniques including single crystal XRD (7b) and in-vitro screened for their antiproliferative potential against human gastric adenocarcinoma (AGS) cells. Most of the synthesized compounds have exhibited excellent cytotoxic results. Twenty analogs were found to have cytotoxic potential better than the reference drug Leucovorin and analog 7j emerged as the most potent with IC50=5.98 mu M nearly one fifth to the standard drug Leucovorin (IC50=30.8 mu M). This library, consisting of twenty three novel and eighteen reported morpholine-functionalized aurones, bearing diverse substitution pattern, further helped in making a concrete structure-activity relationship for antiproliferative potential. Additionally, in-silico molecular docking, Hirshfeld surface analysis and two dimensional fingerprint plots were also studied to understand the molecular interactions and various structural aspects. Further computational investigations of these compounds were conducted using the DFT/B3LYP method, for the determination of HOMO and LUMO energy values as well as the calculation of chemical softness, hardness, electronegativity and electrophilic index etc. We successfully designed and synthesized a library of forty one 7(a-ao) diversely functionalized morpholine tethered aurone analogs. All the synthesized hybrids were also screened for their antiproliferative potential against human gastric adenocarcinoma (AGS) cells. Twenty of the synthesized compounds exhibited IC50 values even lower than the standard drug Leucovorin and the IC50 for analog 7 j (IC50=5.98 mu M) was nearly one fifth to the standard drug Leucovorin (IC50=30.8 mu M). image

This study involves the synthesis of a series of dimethyl substituted novel aurones, featuring 1,2,3-triazole as an integral structure. All the newly synthesized compounds were thoroughly characterized using various spectroscopic tools and also subjected to computational analysis utilizing the DFT/B3LYP methodology, which involved the determination of frontier molecular orbital energy values and the computation of various quantum chemical parameters. Further their impact on cell viability and cytotoxic activity on the adenocarcinoma gastric cell line (AGS) was investigated using cell-based MTT assay. Compounds 6d, 6o and 6p displayed significant cytotoxic activity, reducing cell viability to a greater extent with IC50 values of 9.74, 20.09, and 5.92 mu M, respectively and even better than the standard chemotherapeutic drug leucovorin (IC50 = 30.8 mu M). In addition, all the compounds were also screened for their extracellular enzymatic assay and through in vitro results compound 6n emerged as the efficient inhibitor of amylase (% inhibition = 51.92) and trypsin (% inhibition = 68.36), whereas an activation is observed for lipase (% activation = 269.48). In silico molecular docking was also conducted to assess the interactions between proteins and ligands, revealing the binding patterns of the synthesized compounds and the standard drug with receptor proteins.

Background: The increasing utilization of spiro compounds in drug discovery, led us to design and synthesize regioselectively some novel dispiroheterocycles, by a standard 1,3-dipolar cycloaddition reaction between 6-hydroxyaurone and in situ generated azomethine ylides, using ultra-sonication as green energy source. These results are first of its kind in the literature reported so far for the similar conditions. After confirmation of the proposed structures spectroscopically, using 1H NMR, 13C NMR and FT-IR spectral data, all the compounds are screened for their potential biological activities. Methods: Three component protocol, that contain (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one, sarcosine and unsubstituted isatin. In which azomethine ylides react with olefinic dipolarophiles through 1,3-dipolar cycloaddition, which is highly regio- and stero-selective way in situ. Structures of the proposed products have been confirmed using 1H NMR, 13C NMR and FT-IR spectral data. Results: In order to screen the potential biological activities of the synthesized compounds, their effect was observed on trypsin, amylase and lipase activities. Differential effect has been observed. Trypsin was substantially activated whereas an inhibitory effect was observed for amylase and lipase supported by insilico studies. Conclusion: Synthesis of six novel 6-hydroxy-1'-methyl-4'-phenyl-3H-dispiro[benzofuran-2,3'- pyrrolidine-2',3''-indoline]-2'',3-dione derivatives have been made using a multicomponent greener protocol. These synthesized compounds have exhibited differential effects toward trypsin, amylase and lipase well supported by in-silico studies. Thus, the present study highlights their potential use as antiinflammatory and anti-obesity agents.

A Schiff base ligand named 4-(((5-mercapto-4H-1,2,4-triazole-4-yl)imino)methyl)-(benzyloxy)benzene (HL) and its bioactive series of Ni(II), Cu(II), Zn(II) and Cd(II) metal complexes having 1:1 and 2:1 ligand-to-metal ratio, have been synthesized. All the synthesized compounds were fully characterized by IR, 1H-NMR, elemental analysis, absorbance (UV-Vis.) and mass spectra. Furthermore, the molecular structure of the Schiff base was established by single-crystal X-ray diffraction analysis. Additionally, computational investigations of the compounds were conducted using the DFT/B3LYP method. This analysis involved the determination of FMO energy values, as well as the calculation of quantum chemical parameters. The binding effect of metal ions on the ligand's fluorescence intensity was probed using fluorescence spectroscopy. The thermal stability and kinetic parameters of the complexes were determined using TGA (Thermogravimetric Analysis) analysis via the Coats-Redfern method. The docking studies, actively explored the interaction between Schiff base ligand and protein receptor molecules of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. To assess the therapeutic potential, an in silico ADMET model was employed, revealing that the synthesized molecules exhibit drug-like properties. The Schiff base and all the derived metal complexes were screened for their antimicrobial potential against bacterial species like Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and fungus Candida albicans.

ZrO2 is a versatile heterogeneous catalyst due to its good stability, unique surface properties and by the existence of acidic/basic and oxidising/reducing properties. To explore the ZrO2 characteristics, numerous synthesis and modification strategies are employed. The present review covered the ZrO2 synthesis, characteristics, modifications and application in organic transformation. In the modifications, metal doping, non-metal doping and composites are discussed in detail. ZrO2 exists in the three crystalline structures depending upon the calcination temperature. This review focuses on the effect of temperature and various synthesis approaches to fabricate the ZrO2 with different crystalline structures. In heterogeneous catalysis, surface characteristics are primarily important, therefore, alteration in the surface features, especially morphology and surface area by varying synthesis parameters is also covered here. In the later part, a variety of organic reactions catalysed by ZrO2, effect of ZrO2 and its composite on the product yield and kinetics of organic reaction is explored in this review.

Enzymes are the biological macromolecules that have emerged as an important drug target as their upregulation/ imbalance leads to various pathological conditions, such as inflammation, parasitic infection, Alzheimer's, cancer, and many others. Here, we designed and synthesized some morpholine tethered novel aurones and evaluated them as potential inhibitors for CTSB, & alpha;-amylase, lipase and activator for trypsin. All the newly synthesized compounds were fully characterized by various spectroscopic techniques (1H NMR, 13C NMR, HRMS) and the Z-configuration to them was assigned based on single crystal XRD data and 1H NMR chemical shift values. Further, the hybrids were evaluated for their intracellular (cathepsin B) and extracellular (trypsin, lipase, amylase) enzyme inhibition potencies. The in -vitro inhibition screening against cathepsin B revealed that most of the synthesized compounds are good competitive inhibitors (% inhibition = 22.91-75.04), with 6q (% inhibition = 75.04) and 6r (% inhibition = 71.13) as the eminent inhibitors of the series. At the same time, they exhibited weak to moderate inhibition towards amylase (% inhibition = 7.22-22.48) and lipase (% inhibition = 16.29-54.83). A significant trypsin activation (% activation = 107.42-196.47) was observed even at the micromolar concentration of the compounds. Furthermore, the drug-modeling studies showed a good correlation between the in-vitro experimental results and the calculated binding affinity of the screened compounds with all the tested enzymes. These findings are expected to provide a new lead in drug development for different pathological disorders wherever these enzymes are involved.

In this article, for a class of stochastic pure-feedback nonlinear systems with simultaneous actuator and sensor faults, the problem of adaptive fault-tolerant control is examined. The stochastic pure-feedback nonlinear system is first converted into a strict-feedback by applying the mean value theorem and radial basis function neural networks are used to approximate the unknown functions. Only one adaptive parameter needs to be calculated online rather than the actual weight vector elements by determining the greatest value of the norm of the neural network weight vector. With the help of regrouping and parameter separation methods, the unavailability of state variables caused by sensor faults is addressed. The Lyapunov function methods and the backstepping recursive design technique are used to design an adaptive fault-tolerant controller. It is shown that by choosing proper the design parameters, the tracking errors converge to a small region of the origin, and all the signals in the closed-loop system are bounded in probability. The performance of the proposed controller is illustrated using a numerical example and a real-world example of a rigid robot manipulator system.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

OBJECTIVE The end-to-end (E2E) testing method enables understanding the difficulties and uncertainties in treating any specific case type. This study was focused on bilateral metallic implant cases. METHODS The study was performed on a cylindrical phantom of Perspex with holes for implant inserts. Two stainless steel metal rods of 7.5-8.0 g/cc mass density were inserted in the phantom. The ionization chamber CC13 was kept at a 5 cm depth in the phantom. The phantom was scanned on a computed tomography simulator in pelvis protocol with a 1mm slice thickness. The scans were imported to the contouring station without applying artifacts correction. Chamber volume was contoured as gross tumor volume (GTV); margin to GTV, clinical target volume, and planning target volume were created. Four isocentric plans (Conventional, three-dimensional conformal radiotherapy[3D-CRT], intensity-modulated radiotherapy [IMRT], and volumetric-modulated radiotherapy [VMAT]) were generated for two LinacsTruebeam (TB)-sTx and 2300-CD. The conventional plan was a single anterior field, 3D-CRT was four field box techniques, IMRT was seven field plan, and VMAT was with two complete arc. Pre-treatment verification was done using CBCT. Four plans were created on helical tomotherapy with different prescriptions and delivered using MVCT guidance. RESULTS In conventional plans, variations were -1.40%, -1.57%, and for 3DCRT, variations were -5.08% and -4.93%, for IMRT, the differences between measured and TPS doses were 1.84 % and -1.55% for VMAT plans, and the variations were 0.68% and -0.88% for TB and 2300-CD, respectively. The tomotherapy plans with gradient showed deviations more significant than 3%. Similarly, the variations for single prescription plans were within 3%. CONCLUSION The phantom design used in the test provided a comprehensive understanding of simulation and delivery problems.

Diagnostics of the inductively coupled plasma (ICP) generated using a flat spiral antenna are performed using radio frequency (RF) compensated Langmuir probe (CLP). The measurements on the generated plasma are made under the varying influence of the RF self-biased substrate electrode immersed in the plasma. From the $V$ – $I$ characteristics of the Langmuir probe taken at different radial locations in the plasma volume at a fixed axial distance of 5 cm from the quartz isolation window, electron energy probability functions (EEPFs) at various locations are obtained. It is observed that there is a strong correlation between the plasma parameters and EEPF with the bias on the substrate electrode. At a constant RF power in antenna coils, the EEPF evolved from bi-Maxwellian to Maxwellian with an increase in the bias level on the substrate electrode. The evolution of the EEPF with a variation of operating pressure is explained in terms of different heating mechanisms in plasma. Furthermore, EEPF evolution in the plasma from Maxwellian to bi-Maxwellian under the varying influence of RF power fed to the antenna coils keeping RF self-bias level on the substrate electrode constant is also explained.

The stock price fluctuation of one country can be influenced by the movement of the stock price of other countries implying that there exists some relationship among various stock markets. This study examines the interrelationship among Asian stock markets and forecasts the stock market on the basis of the relationship that exists among Asian stock markets. The interrelationship is tested by using the Granger causality (GC) test and Pearson's correlation (PC) matrix. Further, a deep learning model namely a long short term memory (LSTM) neural network is utilized to forecast the stock price of one country by using the price of other countries that have a correlation and causal relationship with the target stock market. PC matrix shows that there exists a strong correlation among Asian stock markets. Results from the GC show that there exists a unidirectional relationship between Sensex and NIKKEI 225 to SSE composite index, Sensex to NIKKEI 225, and Sensex and TSEC weighted index to KOSPI composite index and a bi-directional relationship among Sensex, TSEC weighted index and Hang Seng index. Experimental results show that GC and LSTM-based model namely GC-LSTM shows better forecasting performance in comparison to PC and LSTM-based model termed as PC-LSTM.

This work proposes a novel approach to social robot navigation by learning to generate robot controls from a social motion latent space. By leveraging this social motion latent space, the proposed method achieves significant improvements in social navigation metrics such as success rate, navigation time, and trajectory length while producing smoother (less jerk and angular deviations) and more anticipatory trajectories. The superiority of the proposed method is demonstrated through comparison with baseline models in various scenarios. Additionally, the concept of humans' awareness towards the robot is introduced into the social robot navigation framework, showing that incorporating human awareness leads to shorter and smoother trajectories owing to humans' ability to positively interact with the robot.

Metal oxides are a developing class of heterocatalysts that behave as a linker between organic and inorganic chemistry. Metal oxide heterostructures illustrate various striking surface features such as oxidation/reduction capabilities, acidic–basic characteristics, porosity, flexibility, and high readiness of lattice oxygen and make them preferable over homogeneous catalysts. The short reaction time, ease of formation and separation, and their reusability and selectivity all make them a prodigious selection in various pharmaceutical and petrochemical industries. These have been widely used in various organic transformations. This chapter highlights the higher catalytic activity of various metal oxide heterostructures and summarizes their significance in various organic transformations.

Amylase, lipase, and trypsin are crucial digestive enzymes, whose activation or inhibition is of potent therapeutic approach for treating various body disorders. In this work, we have synthesized a small library of pyrrolidine-tethered novel aurones 4(a-k) and structures validated by analyzing their IR, NMR (1H and 13C), and mass spectrometry data. The biological activities of the synthesized aurones were evaluated through in vitro and in silico experiments against digestive enzymes. A distinct pattern emerged, with significant activation observed for trypsin and amylase, while lipase was notably inhibited. Among the synthesized compounds, 4f produced the highest lipase inhibition (72.3%), whereas 4k showed maximum activation for trypsin (EC50 = 0.94×10-6 M) and 4f activated amylase (EC50 = 8.76×10-4 M) to the maximum extent, thus confirming their possible use as agents for combating inflammation and obesity.