In an effort to expand the repertoire of potent alpha-amylase inhibitors, we sought to develop novel inhibitors by combining 1,4-naphthoquinone, 1,2,3-triazole, and N-acyl hydrazone scaffolds in a single matrix. To achieve this, twelve novel naphtho[2,3-d][1,2,3]triazole-4,9-dione tethered N-acyl hydrazones were synthesized through condensation reaction of 2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)acetohydrazide with various substituted aryl aldehydes. Structural elucidation for all the compounds was performed using 1D, 2DNMR, FTIR, and mass spectral analyses. The synthesized molecules were evaluated for their ability to inhibit alpha-amylase activity using acarbose as the standard drug. All the derivatives exhibited potent inhibition of alpha-amylase, with IC50 values ranging between 17.26 +/- 0.07 to 25.62 +/- 0.03 mu g/mL. Notably, compound 9c possessing - meta substituted -NO2 group displayed the highest activity (IC50 = 17.26 +/- 0.07 mu g/mL) among the series. Structure-activity relationship (SAR) revealed the pivotal role of aryl ring substitutions in determining inhibitory efficacy. To validate these findings and to assess the binding stability of 9c within the catalytic site alpha-amylase dervied for A. oryzae ( PDB ID: 7TAA), in silico studies were performed. The compound 9c effectively occupies the enzyme's active pocket, with minimal RMSD fluctuations observed over 100 ns simulation, indicating stable protein-ligand complex. ADMET predictions suggested favorable drug-like properties, underscoring the potential of these compounds as novel alpha-amylase inhibitors for managing type 2 diabetes mellitus

This investigation delves into diverse attributes of environmentally friendly nickel-doped zinc oxide and neodymium doped zinc oxide nanoparticles. It focuses on evaluating their effectiveness in photocatalysis, antibacterial activity and antioxidant properties. Utilizing a sustainable synthesis approach incorporating phytochemicals from Vitex negundo, hexagonal structures of both nickel-doped zinc oxide and neodymium-doped zinc oxide nanoparticles were confirmed through X-ray diffraction analysis. Transmission electron microscopy and scanning electron microscopy-energy dispersive X-ray spectroscopy analyses identified spherical nanoparticles with size between 8 and 15 nanometers. Photocatalytic assessments using methyl green dye degradation demonstrated promising results for both nickel-doped zinc oxide and neodymium-doped zinc oxide nanoparticles. Antibacterial tests showcased nanoparticle's ability to disrupt Bacillus subtilis and Escherichia coli, with neodymium doped zinc oxide nanoparticles exhibiting superior antibacterial activity. Antioxidant potential, evaluated through 2,2-diphenyl-1-picrylhydrazyl free radical assay, highlighted nanoparticles radical-scavenging ability, with neodymium doped zinc oxide nanoparticles showing enhanced activity due to phytochemicals introduced during green synthesis. This research innovates through green synthesis of nickel-doped zinc oxide and neodymium-doped zinc oxide nanoparticles, capitalizing on their distinctive properties for synergistic applications. The study provides valuable insights into potential future applications, offering novel solutions for environmental remediation and biomedical purposes.

A new series of thiazolidine-2,4-dione tethered 1,2,3-triazole derivatives were designed, synthesized and screened for their alpha-amylase inhibitory potential employing in vitro and in silico approaches. The target compounds were synthesized with the help of Cu (I) catalyzed [3 + 2] cycloaddition of terminal alkyne with numerous azides, followed by unambiguously characterizing the structure by employing various spectroscopic approaches. The synthesized derivatives were assessed for their in vitro alpha-amylase inhibition and it was found that thiazolidine-2,4-dione derivatives 6e, 6j, 6o, 6u and 6x exhibited comparable inhibition with the standard drug acarbose. The compound 6e with a 7-chloroquinolinyl substituent on the triazole ring exhibited significant inhibition potential with IC50 value of 0.040 mu mol mL-1 whereas compound 6c (IC50 = 0.099 mu mol mL-1) and 6h (IC50 = 0.098 mu mol mL-1) were poor inhibitors. QSAR studies revealed the positively correlating descriptors that aid in the design of novel compounds. Molecular docking was performed to investigate the binding interactions with the active site of the biological receptor and the stability of the complex over a period of 100 ns was examined using molecular dynamics studies. The physiochemical properties and drug-likeliness behavior of the potent derivatives were investigated by carrying out the ADMET studies.

This study aimed to synthesize thiazolidine-2,4-dione hybrids followed by evaluating their α-amylase inhibition using in vitro and in silico approaches.

In our quest to design and develop N/O-containing inhibitors of α-amylase, we have tried to synergize the inhibitory action of 1,4-naphthoquinone, imidazole and 1,2,3-triazole motifs by incorporating these structures into a single matrix. For this, a series of novel naphtho[2,3-d]imidazole-4,9-dione appended 1,2,3-triazoles is synthesized by a sequential approach involving [3 + 2] cycloaddition of 2-aryl-1-(prop-2-yn-1-yl)-1H-naphtho[2,3-d]imidazole-4,9-diones with substituted azides. The chemical structures of all the compounds are established with the help of 1D-NMR, 2D-NMR, IR, mass and X-ray studies. The developed molecular hybrids are screened for their inhibitory action on the α-amylase enzyme using the reference drug, acarbose. Different substituents present on the attached aryl part of the target compounds show amazing variations in inhibitory action against the α-amylase enzyme. Based on the type of substituents and their respective positions, it is observed that compounds containing -OCH3 and -NO2 groups show more inhibition potential than others. All the tested derivatives display α-amylase inhibitory activity with IC50 values in the range of 17.83 ± 0.14 to 26.00 ± 0.17 μg/mL. Compound 2-(2,3,4-trimethoxyphenyl)-1-{[1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl]methyl}-1H-naphtho[2,3-d]imidazole-4,9-dione (10y) show maximum inhibition of amylase activity with IC50 value 17.83 ± 0.14 μg/mL as compared to reference drug acarbose (18.81 ± 0.05 μg/mL). A molecular docking study of the most active derivative (10y) is performed with A. oryzae α-amylase (PDB ID: 7TAA) and it unveils favourable binding interactions within the active site of the receptor molecule. The dynamic studies reveal that the receptor-ligand complex is stable as the RMSD of less than 2 is observed in 100 ns molecular dynamic simulation. Also, the designed derivatives are assayed for their DPPH free radical scavenging ability and all of them exhibit comparable radical scavenging activity with the standard, BHT. Further, to assess their drug-likeness properties, ADME properties are also evaluated and all of them demonstrate worthy in silico ADME results.

Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 μmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes.

Urease has a long and distinguished history in the development of enzymology since it was the first enzyme crystallized by Sumner in 1926. The present review article is focused on the urease inhibitory potential of thiazolidinone, triazole, and benzothiazole-based heterocyclic derivatives. The study begins with the historical developments in the discovery of urease and its substrate, urea, along with the active site architecture of ureases of different origins. The two pathways for the urease-catalyzed hydrolysis of urea are explained in detail. The urease inhibitory potential of the aforementioned heterocyclic derivatives is reviewed and arranged systematically. Structure-activity relationships (SARs) study provided the substituents necessary for urease inhibition and will be useful for the researchers working in the field of anti-ulcer agents. To a step further, important binding interactions were identified with the amino acid residues at the active site of the enzyme. The information gathered is anticipated to offer logical direction and an effective method for creating innovative, potent, and efficient urease inhibitors that will have greater practical uses in the future.

We were encouraged to design and produce a new series of chalcone derivatives since there is a critical need for novel anticancer drugs with high selectivity for cancer cells. Chalcones are members of the flavonoid family that act as precursors in the production of flavonoids, which are plentiful in plants. Chalcones are significant starting points for synthetic modifications and serve as mediators in the synthesis of critical therapeutic compounds. Cancer is one of the leading causes of death globally. New compounds still need to be found to cure cancer. In certain cancer cells, chalcone and its derivatives have anticancer potential. Modern medication design frequently uses molecular docking to understand drug-receptor interaction. Docking studies are a crucial technique for enabling the organised use of the structural variety of natural products. The Molegro Virtual Docker 6.0 was used in this work to conduct docking investigations on natural anticancer drugs that contained chalcone. Using the software Molegro Virtual Docker 6.0, we docked the protein crystal structure of human T-cell leukaemia virus protease (2B7F) with several chalcone-based derivatives (AMP-1-56) for our study project. Among the compounds AMP-56, compounds AMP-40, 44, 45, 48, 49, 52, 55 and 56 exhibit good anticancer activity with human T-cell leukaemia virus protease (PDB-2B7F) as compared to the reference drug (Camptothecin). The results are still preliminary, and an experimental evaluation will soon be performed.

alpha-Amylase (EC.3.2.1.1) is a ubiquitous digestive endoamylase. The abrupt rise in blood glucose levels due to the hydrolysis of carbohydrates by alpha-amylase at a faster rate is one of the main reasons for type 2 diabetes. The inhibitors prevent the action of digestive enzymes, slowing the digestion of carbs and eventually assisting in the management of postprandial hyperglycemia. In the course of developing alpha-amylase inhibitors, we have screened 2-aryliminothiazolidin-4-one based analogs for their in vitro alpha-amylase inhibitory potential and employed various in silico approaches for the detailed exploration of the bioactivity. The DNSA bioassay revealed that compounds 5c, 5e, 5h, 5j, 5m, 5o and 5t were more potent than the reference drug (IC60 value = 22.94 +/- 0.24 mu g mL-1). The derivative 5o with -NO2 group at both the rings was the most potent analog with an IC60 value of 19.67 +/- 0.20 mu g mL-1 whereas derivative 5a with unsubstituted aromatic rings showed poor inhibitory potential with an IC60 value of 33.40 +/- 0.15 mu g mL-1. The reliable QSAR models were developed using the QSARINS software. The high value of R2ext = 0.9632 for model IM-9 showed that the built model can be applied to predict the alpha-amylase inhibitory activity of the untested molecules. A consensus modelling approach was also employed to test the reliability and robustness of the developed QSAR models. Molecular docking and molecular dynamics were employed to validate the bioassay results by studying the conformational changes and interaction mechanisms. A step further, these compounds also exhibited good ADMET characteristics and bioavailability when tested for in silico pharmacokinetics prediction parameters.

Aim: The primary objective of this investigation was the synthesis, spectral interpretation and evaluation of the α-amylase inhibition of rationally designed thiazolidinedione-triazole conjugates (7a-7aa). Materials & methods: The designed compounds were synthesized by stirring a mixture of thiazolidine-2,4-dione, propargyl bromide, cinnamaldehyde and azide derivatives in polyethylene glycol-400. The α-amylase inhibitory activity of the synthesized conjugates was examined by integrating in vitro and in silico studies. Results: The investigated derivatives exhibited promising α-amylase inhibitory activity, with IC50 values ranging between 0.028 and 0.088 μmol ml-1. Various computational approaches were employed to get detailed information about the inhibition mechanism. Conclusion: The thiazolidinedione-triazole conjugate 7p, with IC50 = 0.028 μmol ml-1, was identified as the best hit for inhibiting α-amylase.

The present manuscript describes the synthesis, alpha-amylase inhibition, in silico studies and in-depth quantitative structure-activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. alpha-Amylase inhibitory potential of all compounds has been explored, where compound 7n exhibits remarkable alpha-amylase inhibition of 87.5% at 50 mu g/mL. Robust QSAR models are made by using the balance of correlation method in CORAL software. The chemical structures at different concentration with optimal descriptors are represented by SMILES. A data set of 66 SMILES of 22 hydrazones at three distinct concentrations are prepared. The significance of the index of ideality of correlation (IIC) with applicability domain (AD) is also studied at depth. A QSAR model with best R-validation(2)= 0.8587 for split 1 is considered as a leading model. The outliers and promoters of increase and decrease of endpoint are also extracted. The binding modes of the most active compound, that is, 7n in the active site of Aspergillus oryzae alpha-amylase (PDB ID: 7TAA) are also explored by in silico molecular docking studies. Compound 7n displays high resemblance in binding mode and pose with the standard drug acarbose. Molecular dynamics simulations performed on protein-ligand complex for 100 ns, the protein gets stabilised after 20 ns and remained below 2 angstrom for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to C alpha carbon atom is insignificant. [GRAPHICS] .

Monte Carlo optimization based QSGFEAR model development using CII results in the formation of more reliable, robust and predictive models.

NMR based in-depth exploration of stereodynamic behavior in equilibrating E / Z 2-aryliminothiazolidin-4-ones and determination of kinetic and thermodynamic parameters.

In the present era of the industrial revolution, we all are familiar with ever-increasing environmental pollution released from various chemical processes. Chemical production has had a severe impact on the environment and human health. For the betterment of our environment, the chemical community has turned their interest to developing green, harmless and sustainable synthetic processes. To accomplish these goals of green chemistry, the extraordinary properties of sonication play an important role. It is well known that sonochemistry can make decisive contributions to creating high pressures of almost 1000 atm and very high temperatures in the range of 4500–5000 °C. The implementation of ultrasound in chemical transformations somehow fulfils the measures of green chemistry, as it reduces energy consumption, enhances product selectivity, and uses lesser amounts of hazardous chemicals and solvents. Furthermore, heterocyclic synthesis under ultrasonication offers several environmental and process-related advantages compared with conventional methods. The remarkable contribution of ultrasonics to the development of green and sustainable synthetic routes inspired us to write this article. Herein, we have discussed only some of the various synthetic methodologies developed for the construction of heterocyclic cores under ultrasonic irradiation, accompanied by mechanistic insights. In some cases, a comparison between sonochemical conditions and conventional conditions has also been investigated. We emphasized principally ‘up to date’ developments on various sono-accelerated chemical transformations comprising aza-Michael, aldol reactions, C–C couplings, oxidation, cycloadditions, multi-component reactions, etc. for the synthesis of heterocycles.

The 1,4-naphthoquinone skeleton is an important pharmacophoric unit found in many biologically active natural products and many well-known chemotherapy agents, such as alkannin, shikonin, and doxorubicin. Among naphthoquinones, 1,4-naphthoquinones with electron donor amino substituents on 2- and 3- positions are captodatively substituted biradicaloids and owing to their redox-active nature, are greatly renowned for their ability to act as potential anion sensors in the detection of various anions. Besides this, they possess a wide variety of biological and industrial applications. 2,3-Diamino-1,4-naphthoquinone, a potential bacteriostatic agent, acts as a promising lead candidate in the development of various biologically active molecules. Owing to the enthralling synthetic importance and aforementioned pharmacological applications of 1,4-naphthoquinone derivatives, our interest is turned into a detailed study of these privileged pharmacophoric structures. The present review gives an updated vision of various biological and photophysical properties possessed by designed derivatives along with their synthesis. (c) 2022ElsevierB.V. Allrightsreserved.

Benzothiazole and its derivatives have been manifested as an optimistic scaffold due to their immense biological importance. Several methodologies have been reported as modifications after the first report of 2-substituted benzothiazole. Among them, many involve a shift from the conventional synthetic approach by utilizing different catalytic systems. Moreover, synthetic methodologies focused on improvements in terms of product yield, reaction duration, use of environmentally benign conditions and simplified workup procedures predominate among the recently developed approaches. Solid-phase organic synthesis received considerable attention with the pioneering findings of Merrifield's solid-phase peptide synthesis in 1963. A diverse range of organic, inorganic and organic-inorganic substances have been utilized as polymeric solid supports in various catalytic applications. The recyclability and reusability of the immobilized catalysts over consecutive cycles establish them as an attractive alternative over conventional catalytic systems from the environment as well as industrial perspective. The present review summarizes the recent developments in the environmentally benign synthesis of benzothiazole derivatives using supported reagents. Different solid supports along with their catalytic application, mechanistic perspective and substrate tolerance have been discussed comprehensively.

In an effort to explore a class of novel antidiabetic agents, we have made an effort to synergize the α-amylase inhibitory potential of 1,3-benzothiazole and 1,3,4-oxadiazole scaffolds by combining the two into a single structure via an ether linkage. The structure of synthesized benzothiazole clubbed oxadiazole derivatives are established by different spectral techniques. The synthesized hybrids are evaluated for their in vitro inhibitory potential against α-amylase. Compound 8f is found to be the most potent with a significant inhibition (87.5 ± 0.74% at 50 μg/mL, 82.27 ± 1.85% at 25 μg/mL and 79.94 ± 1.88% at 12.5 μg/mL) when compared to positive control acarbose (77.96 ± 2.06%, 71.17 ± 0.60%, 67.24 ± 1.16% at 50 μg/mL, 25 μg/mL and 12.5 μg/mL concentration). Molecular docking of the most potent enzyme inhibitor, 8f, shows promising interaction with the binding site of biological macromolecule Aspergillus oryzae α-amylase (PDB ID: 7TAA) and human pancreatic α-amylase (PDB ID: 3BAJ). To a step further, in-depth QSAR studies show a significant correlation between the experimental and the predicted inhibitory activities with the best Rvalidation2 = 0.8701. The developed QSAR model can provide ample information about the structural features responsible for the increase and decrease of inhibitory activity. The mechanistic interpretation of the structure-activity relationship (SAR) is done with the help of combined computational calculations i.e. molecular docking and QSAR. Finally, molecular dynamic simulations are performed to get an insight into the binding mode of the most potent derivative with α-amylase from A. oryzae (PDB ID: 7TAA) and human pancreas (PDB ID: 3BAJ).

Research often leads to unprecedented results that open the gates for new methodologies. We report herein the oxidative aromatization and serendipitous regioselective nitration of 1,3,5-trisubstituted-4,5-dihydro-1H-pyrazoles under mild reaction conditions using SiO2-HNO3 as an oxidizing agent to afford 1,3,5-trisubstituted pyrazoles with high regioselectivity. Here SiO2-HNO3 acts as a nitrating agent along with oxidizing property. SiO2-HNO3 is cheap, easy to prepare, eco-friendly and practically applicable catalyst.

In search of potent alpha-amylase inhibitors, herein we report the synthesis, molecular docking and QSAR study of some thiazole clubbed pyrazole hybrids (TCPH) i.e., 1-((1-phenyl-3-aryl-1H-pyrazole-4-yl)methylene)-2-(4-arylthiazole-2-yl)hydrazine (4a-4r) as an alpha-amylase inhibitors. Among the different analogues, compounds 4g and 4h were found to be most potent at 50 mu g/mL with 89.15% and 88.42% of inhibition. The Monte Carlo optimisation method was applied to build robust QSAR models for the prediction of percentage inhibition of TCPH at different concentration with various statistical parameters. The Simplified Molecular Input Line Entry System (SMILES) was applied to symbolise the molecular structure, descriptor calculation and model development. The role of the index of ideality correlation (IIC) was also studied which revealed a model for split 3 as a leading model with best R-2 i.e., 0.9198. The compound 4l at different concentration (TCPH11, TCPH29 and TCPH47) was outside the applicability domain (AD) for the developed QSAR models for split 4 only. The SMILES attributes at three different concentrations were also detected. These attributes are the promoters of percentage increase/decrease in inhibition efficiency of the inhibitors. The docking simulation of most active compounds (4g and 4h) were performed within the active site of Aspergillus oryzae alpha-amylase (PDB ID: 7TAA) to analyse the binding conformation and interactions responsible for their activity. As a result, it was found that the binding interactions found between 4g, 4h and alpha-amylase were similar to those responsible for alpha-amylase inhibition by acarbose. Communicated by Ramaswamy H. Sarma