Pushing Boundaries: What's Next in Metal-Free C-H Functionalization for Sulfenylation?

The synthesis of thioether derivatives has been explored widely due to the potential application of these derivatives in medicinal chemistry, pharmaceutical industry and material chemistry. Within this context, there has been an increasing demand for the environmentally benign construction of C-S bonds via C-H functionalization under metal-free conditions. In the present article, we highlight recent developments in metal-free sulfenylation that have occurred in the past three years. The synthesis of organosulfur compounds via a metal-free approach using a variety of sulfur sources, including thiophenols, disulfides, sulfonyl hydrazides, sulfonyl chlorides, elemental sulfur and sulfinates, is discussed. Non-conventional strategies, which refer to the development of thioether derivatives under visible light and electrochemically mediated conditions, are also discussed. The key advantages of the reviewed methodologies include broad substrate scope and high reaction yields under environmentally benign conditions. This comprehensive review will provide chemists with a synthetic tool that will facilitate further development in this field.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity.

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

Computational and optoelectronic investigations of red-emissive europium (III) ß-diketonate with n-donor ligands for display applications.

Europium complexes exhibiting red luminescence were prepared by employing ß-diketone as main ligand and 1,10-phenanthroline as an additional ligand. Various methods, including 1H NMR, IR spectroscopy and analysis of optical band gap were employed to examine these complexes. The luminescent photophysical properties were investigated using PL spectroscopy and theoretical calculations were conducted to explore radiative transitions probabilities and Judd-Ofelt (J-O) parameters for transitions of type 5D0 → 7F2, 4. J-O parameters were determined using the JOES computer program and results were in good agreement with the outcomes obtained experimentally. The luminescence analysis results have verified the vibrant, single-color red emission of the prepared complexes. The band gap of ternary europium complexes, determined optically, electronically, and theoretically, falls within the range of 3-4 eV. This similarity indicates that these complexes are potentially suitable as semiconductor materials. The results from absorption, electrochemical and photophysical analyses indicate the potential use of synthesized complexes in lighting and display applications.

CORAL: probing the structural requirements for α-amylase inhibition activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives based on QSAR with correlation intensity index, molecular docking, molecular dynamics, and ADMET studies.

The present study aims to examine the structural requirements governing α-amylase inhibitory activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives and their precursors by employing a multifaceted approach combining in vitro and in silico studies. The in vitro assay findings revealed strong inhibitory effect of this class of compounds against α-amylase and compound 20 exhibited maximum percentage inhibition of 88.54 ± 0.69, 84.98 ± 0.40, 77.26 ± 0.75, 67.80 ± 0.54, and 62.93 ± 1.17 at 200, 100, 50, 25, and 12.5 µg mL-1, respectively. Multiple CORAL QSAR models were developed from the randomly distributed eight splits by employing two target functions (TF1, TF2 with WCII = 0.0 and = 0.3, respectively), and the quality of predictions by the produced models was validated with the help of various statistical parameters. The model M-4 (R2Val = 0.8799) and model M-11 (R2Val = 0.9064) were the leading models developed by using TF1 and TF2. We designed five new congeneric inhibitors (D-1 to D-5) by incorporating SMILES features positively correlating with the activity. Molecular docking experiments were carried out to confirm the binding of these new inhibitors with the biological receptor α-amylase (PDB ID: 7TAA). Furthermore, molecular dynamic simulations provided a thorough knowledge of the binding process by shedding insight into the dynamic behavior and stability of the ligand-receptor complex over time. The results of this study highlight the key structural characteristics needed for improved α-amylase inhibitory efficacy and provide a rational basis for the development of more effective inhibitors.Communicated by Ramaswamy H. Sarma.

α-amylase inhibition and in silico studies of novel naphtho[2,3-d]imidazole-4,9-dione linked N-acyl hydrazones.

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.

Thiazolidinedione-triazole conjugates: design, synthesis and probing of the α-amylase inhibitory potential.

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.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile.

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective.

Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in "housekeeping" roles, the expression of the COX-II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic anti-inflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.

Development of thiazole-appended novel hydrazones as a new class of α-amylase inhibitors with anticancer assets: an in silico and in vitro approach.

Hyperamylasemia is reported to be associated with numerous chronic diseases, including diabetes and cancer. Considering this fact, we developed a series of thiazole-clubbed hydrazones. The derivatives were explored for their in vitro α-amylase inhibitory activity, which was further corroborated with their anticancer assets using a panel of cancer cells, including colon cancer (HCT-116), lung cancer (A549), and breast cancer (MDA-MB-231). To better understand pharmacokinetics, the synthetic derivatives were subjected to in silico ADMET prediction. The in vitro based biological investigation revealed that compared to the reference drug acarbose (IC50 = 0.21 ± 0.008 µM), all the synthesized compounds (5a-5aa) exhibited in vitro α-amylase inhibitory response in the range of IC50 values from 0.23 ± 0.003 to 0.5 ± 0.0 µM. Along with this, the proliferations of the HCT-116, A549 and MDA-MB-231 cells were inhibited when treated with the synthesized compounds. Notable cancer cell growth inhibition was observed for compounds 5e, 5f and 5y, which correlated with their α-amylase inhibition. Additionally, the kinetics investigation revealed that 5b, 5e, 5f and 5y exhibit uncompetitive inhibition. 5b was found to be the least cytotoxic and most potent α-amylase inhibitor and was further validated by absorption and fluorescence quenching technique.

Quantitative structure activity relationship studies of androgen receptor binding affinity of endocrine disruptor chemicals with index of ideality of correlation, their molecular docking, molecular dynamics and ADME studies.

Endocrine disrupter chemicals (EDCs) are both natural and man-made chemicals that mimic, block or interfere with human hormonal system. In the present manuscript, QSAR modeling was performed for the androgen disruptors that interfere with biosynthesis, metabolism or action of androgens that causes adverse effects on male reproductive system. A set of 96 EDCs that exhibited affinity towards androgen receptors (Log RBA) in rats were employed for carrying out QSAR studies using Hybrid descriptors (combination of HFG and SMILES) through Monte Carlo Optimization. Using index of ideality of correlation (TF2), five splits were formed and predictability of five models resulting from these splits was assessed by various validation parameters. Models resulted from first split was the top most one with R2validation = 0.7878. Structural attributes responsible for change in endpoint were studied by employing correlation weights of structural attributes. In order to further validate the model, new EDCs were designed using these attributes. In silico molecular modelling studies were performed to assess the detailed interactions with the receptor. The binding energies of all the designed compounds were observed to be better than lead and are in the range of -10.46 to -14.80. Molecular dynamics simulation of 100 ns was performed for ED01 and NED05. The results revealed that the protein-ligand complex bearing NED05 was more stable than lead ED01 exhibiting better interactions with the receptor. Further, in an attempt to assess their metabolism, ADME studies were evaluated using SwissADME. The developed model enables to predict the characteristics of designed compounds in an authentic way.Communicated by Ramaswamy H. Sarma.

Design, synthesis, spectroscopic characterization, single crystal X-ray analysis, in vitro α-amylase inhibition assay, DPPH free radical evaluation and computational studies of naphtho[2,3-d]imidazole-4,9-dione appended 1,2,3-triazoles.

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.

Parsing structural fragments of thiazolidin-4-one based α-amylase inhibitors: A combined approach employing in vitro colorimetric screening and GA-MLR based QSAR modelling supported by molecular docking, molecular dynamics simulation and ADMET studies.

α-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 α-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 α-amylase inhibitors, we have screened 2-aryliminothiazolidin-4-one based analogs for their in vitro α-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 µg 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 µg mL-1 whereas derivative 5a with unsubstituted aromatic rings showed poor inhibitory potential with an IC60 value of 33.40 ± 0.15 µg 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 α-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.

Correction: Electro-organic synthesis: an environmentally benign alternative for heterocycle synthesis.

Correction for 'Electro-organic synthesis: an environmentally benign alternative for heterocycle synthesis' by Suman Devi, et al., Org. Biomol. Chem., 2022, 20, 5163-5229.

Electro-organic synthesis: an environmentally benign alternative for heterocycle synthesis.

Heterocyclic compounds are considered to be one of the most established structural classes due to their extensive application in agrochemicals, pharmaceuticals and organic materials. Over the past few years, the development of heterocyclic compounds has gone through a considerable renaissance from conventional traditional methodologies to non-conventional electro-organic synthesis. Replacing metal catalysts, strong oxidants and multi-step methodologies with metal and strong oxidant-free single-step protocols has revolutionized the field of sustainable organic synthesis. Electro-organic synthesis has evolved as a scalable and sustainable approach in different synthetic protocols in an environment-benign manner. The current review outlines the recent developments in C-C, C-N, C-S and C-O/Se bond formation for heterocycle synthesis using electrochemical methods. Different synthetic strategies and their detailed mechanistic description are presented to enlighten the future applications of electrochemistry in heterocycle synthesis.

Sonochemical Protocols for Heterocyclic Synthesis: A Representative Review.

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.

Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation.

The present manuscript describes the synthesis, α-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. α-Amylase inhibitory potential of all compounds has been explored, where compound 7n exhibits remarkable α-amylase inhibition of 87.5% at 50 µg/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 Rvalidation2 = 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 α-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 Å for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to Cα carbon atom is insignificant.

Exploring biological efficacy of novel benzothiazole linked 2,5-disubstituted-1,3,4-oxadiazole hybrids as efficient α-amylase inhibitors: Synthesis, characterization, inhibition, molecular docking, molecular dynamics and Monte Carlo based QSAR studies.

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).

Recent efforts for drug identification from phytochemicals against SARS-CoV-2: Exploration of the chemical space to identify druggable leads.

Nature, which remains a central drug discovery pool, is always looked upon to find a putative druggable lead. The natural products and phytochemical derived from plants are essential during a global health crisis. This class represents one of the most practical and promising approaches to decrease pandemic's intensity owing to their therapeutic potential. The present manuscript is therefore kept forth to give the researchers updated information on undergoing research in allied areas of natural product-based drug discovery, particularly for Covid-19 disease. The study briefly shreds evidence from in vitro and in silico researches done so far to find a lead molecule against Covid-19. Following this, we exhaustively explored the concept of chemical space and molecular similarity parameters for the drug discovery about the lead(s) generated from in silico-based studies. The comparison was drawn using FDA-approved anti-infective agents during 2015-2020 using key descriptors to evaluate druglike properties. The outcomes of results were further corroborated using Molecular Dynamics studies which suggested the outcomes in alignment with chemical space ranking. In a nutshell, current research work aims to provide a holistic strategic approach to drug design, keeping in view the identified phytochemicals against Covid-19.

Excited-State Intramolecular Hydrogen-Bonding-Assisted Restricted Rotation: A Mechanism for Monitoring Intracellular Viscosity and Distinguishing Malignant, Differentiating, and Apoptotic Cancer Cells.

We have successfully developed a sensor (IP1) that utilizes a confocal-based live-cell imaging technique for distinguishing malignant, differentiating, and under-apoptosis cancer cells. The intracellular viscosity (IVis) is minimum in the cancer cell, intermediate in differentiating cells, and maximum in the apoptotic cells. Therefore, we have developed a molecular rotor (IP1) that can sense the changes in intracellular viscosity. IP1 works on the viscosity-assisted restricted-rotation mechanism and is facilitated by the excited-state intramolecular hydrogen-bonding phenomenon (ESIHB). The use of ESIHB has fine-tuned the viscosity-sensing properties of IP1, which in turn has greatly helped in our quest of distinguishing the malignant, differentiating, and apoptotic cancer cells by the IP1 probe. It was very effective in monitoring apoptosis by increased fluorescence intensity by the confocal live-cell imaging technique. The noncytotoxic behavior, even at 10 µg/mL concentration, is a charming feature of the developed probe. To the best of our knowledge, this is the first report for the ESIHB-based fluorescence probe that can distinguish malignant, differentiating, and apoptotic cancer cells by the use of live-cell imaging techniques.

Synthesis, molecular docking and QSAR study of thiazole clubbed pyrazole hybrid as α-amylase inhibitor.

In search of potent α-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 α-amylase inhibitors. Among the different analogues, compounds 4g and 4h were found to be most potent at 50 µg/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 R2 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 α-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 α-amylase were similar to those responsible for α-amylase inhibition by acarbose.Communicated by Ramaswamy H. Sarma.