Sagar S. Bhayye

Bio: Sagar S. Bhayye is an academic researcher from University of Calcutta. The author has contributed to research in topics: Pharmacophore & Human serum albumin. The author has an hindex of 6, co-authored 12 publications receiving 81 citations.

Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection.

Abstract: Curcumin has been transformed to racemic curcuminoids via an azomethine ylide cycloaddition reaction using isatin/acenaphthoquinone and proline as the reagents. The products were characterized by extensive 1D/2D NMR analysis and single-crystal X-ray crystallographic studies. The enantiomers of one racemic product were separated by HPLC on a Chiralcel OD-H column and were indeed confirmed by the CD spectra of the separated enantiomers.

Pharmacophore generation, atom-based 3D-QSAR, HQSAR and activity cliff analyses of benzothiazine and deazaxanthine derivatives as dual A2A antagonists/MAO‑B inhibitors.

Abstract: Dual inhibition of A2A and MAO-B is an emerging strategy in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this study, atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) and hologram quantitative structure–activity relationship (HQSAR) models were generated with benzothiazine and deazaxanthine derivatives. Based on activity against A2A and MAO-B, two statistically significant 3D-QSAR models (r2 = 0.96, q2 = 0.76 and r2 = 0.91, q2 = 0.63) and HQSAR models (r2 = 0.93, q2 = 0.68 and r2 = 0.97, q2 = 0.58) were developed. In an activity cliff analysis, structural outliers were identified by calculating the Mahalanobis distance for a pair of compounds with A2A and MAO-B inhibitory activities. The generated 3D-QSAR and HQSAR models, activity cliff analysis, molecular docking and dynamic studies for dual target protein inhibitors provide key structural scaffolds that serve as building blocks in designing drug-like molecules for...

Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions

Abstract: Protein misfolding and fibrillation are the fundamental traits in degenerative diseases like Alzheimer's, Parkinsonism, and diabetes mellitus Bioactives such as flavonoids and terpenoids from plant sources are known to express protective effects against an array of diseases including diabetes, Alzheimer's and obesity Andrographolide (AG), a labdane diterpenoid is prescribed widely in the Indian and Chinese health care systems for classical efficacy against a number of degenerative diseases This work presents an in depth study on the effects of AG on protein fibrillating pathophysiology Thioflavin T fluorescence spectroscopy and DLS results indicated concentration dependent inhibition of human serum albumin (HSA) fibrillation The results were confirmed by electron microscopy studies HSA fibril formations were markedly reduced in the presence of AG Fluorescence studies and UV-Vis experiments confirmed further that AG molecularly interacts with HSA at site In silico molecular docking studies revealed hydrogen bonding and hydrophobic interactions with HSA in the native state Thus AG interacts with HSA, stabilizes the native protein structure and inhibits fibrillation The results demonstrated that the compound possesses anti-amyloidogenic properties and can be promising against some human degenerative diseases

Diabetes mellitus caused by mutations in human insulin: analysis of impaired receptor binding of insulins Wakayama, Los Angeles and Chicago using pharmacoinformatics.

Abstract: The University of Pretoria Vice Chancellor’s postdoctoral fellowship and National Research Foundation (NRF), South Africa Innovation postdoctoral fellowship schemes.

Molecular dynamics directed CoMFA studies on carbocyclic neuraminidase inhibitors

Abstract: Zanamivir is the known potent anti-influenza agent targeting the key enzyme neuraminidase that cleaves sialic acid from cell receptors allowing release of newly formed virions. Molecular dynamics simulation was carried out to determine the dynamic behavior of Zanamivir upon its binding to flexible loops of neuraminidase and to analyse its interactions in the bioactive state. Neuraminidase exhibits wide range of affinity with structurally similar compounds. CoMFA study was used to determine quantitative structure-activity relationship for 36 carbocyclic Neuraminidase inhibitors (NIs). The CoMFA model was also successfully built using cross-validated $${{r}^{2}_{\rm cv} =0.580}$$ and $${{r}^{2}_{\rm pred}=0.638}$$ .

Water models for biomolecular simulations

Abstract: Modern simulation and modeling approaches to investigation of biomolecular structure and function rely heavily on a variety of methods—water models—to approximate the influence of solvent. We give a brief overview of several distinct classes of available water models, with the emphasis on the conceptual basis at each level of approximation. The main focus is on classes of models most widely used in atomistic simulations, including popular implicit and explicit solvent models. Among the latter, nonpolarizable N-point models are covered in most detail, including some recent methodological advances and nuances. Notes on practical availability and usage in biomolecular simulations are included. Atomistic simulations that were hardly possible only a short while ago have revealed significant problems that can be traced to deficiencies of most commonly used N-point water models. Recently developed models of this class approximate experimental properties of liquid water much closer than before, and show promise in practical biomolecular simulations. Obstacles to wider adoption of these more accurate water models, both technical and conceptual, are discussed. It is argued that verifying robustness of simulation results to the choice of water model can be of immediate benefit even in the absence of a clear replacement for older models; a specific strategy is proposed. The review is concluded with a discussion on how force-field development efforts can benefit from better solvent models, and vice versa. For further resources related to this article, please visit the WIREs website.

Current Trends towards the Synthesis of Bioactive Heterocycles and Natural Products Using 1,3-Dipolar Cycloadditions (1,3-DC) with Azomethine Ylides

Abstract: This review summarizes the trends in the formation of complex or not so complex heterocyclic structures through 1,3-dipolar cy­cloadditions of azomethine ylides. Diastereo- and enantioselective processes as well as non-asymmetric cycloadditions constitute very important synthetic tools for achieving these compounds. This review covers the literature from 2015 through 2016 and organizes the research in terms of biologically important heterocycles and natural products from cascade 1,3-dipolar cycloadditions of azomethine ylides to the simpler forms of 1,3-dipolar cycloaddition. 1 Introduction 2 Synthesis of Spirooxindoles 3 Synthesis of Spiropyrrolidines 4 Synthesis of Spiropiperidines and Piperidines 5 Synthesis of Pyrrolidines and Fused Pyrrolidines 6 Synthesis of Pyrrolizidines and Indolizidines 7 Synthesis of Quinolone and Isoquinolines 8 Conclusions

A review on biological activities of Schiff base, hydrazone, and oxime derivatives of curcumin

Abstract: Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) is the main pigment present in the turmeric rhizome and shows various biological properties. The synthesis of different derivatives is an effective way to improve the medicinal and biological properties of curcumin. Many researchers have chosen the carbonyl group of curcumin for modification and preparation of new analogues. This review critically surveys a general overview of the literature and summarizes the synthesis and biological activities of Schiff base, hydrazone and oxime derivatives of curcumin over the last decade. These compounds and also their metal complexes possess higher potency in biological activity.

Synthesis of Functionalized 3-Spiro[cyclopropa[a]pyrrolizine]- and 3-Spiro[3-azabicyclo[3.1.0]hexane]oxindoles from Cyclopropenes and Azomethine Ylides via [3 + 2]-Cycloaddition.

Abstract: 3-Spiro[cyclopropa[a]pyrrolizine]- and 3-spiro[3-azabicyclo[3.1.0]hexane]oxindoles were prepared in moderate to high yields via one-pot three-component reactions using substituted isatins, α-amino acids, and cyclopropenes. The key step is an intramolecular [3 + 2]-cycloaddition reaction of an in situ generated azomethine ylide onto a cyclopropene. Both N-substituted and N-unsubstituted α-amino acids, dipeptide Gly-Gly, and also benzylamine were used as the amine component for the azomethine ylide generation. The anticancer activity of some of the obtained compounds against human leukemia K562 cell line was evaluated by flow cytometry in vitro.

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation

Abstract: Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation