Structure-based Assessment of Homologous Analogues of NAtural products -SAHANA: A novel approach to screen bioactive compounds in comparison with their synthetic drug counterparts

Mapping Intimacies ◽

10.21203/rs.3.rs-507920/v1 ◽

2021 ◽

Author(s):

Aditya Rao ◽

Nandini Shetty

Keyword(s):

Natural Products ◽

Dynamics Simulation ◽

Therapeutic Effects ◽

Simulation Studies ◽

Synthetic Drugs ◽

Novel Approach ◽

Disease Condition ◽

Synthetic Drug ◽

Novel Strategy ◽

The Stability

Abstract Background The present study describes a novel strategy to screen natural products (NPs) for their therapeutic effects with predicted most-probable mode of action. The method entitled ‘Structure-based Assessment of Homologous Analogues of NAtural products-SAHANA’ follows a strategy to compare natural products against synthetic drugs based on their molecular properties and 2-dimensional structural similarities. The method is based on a well-established hypothesis that, the molecules with similar structural properties will have similar functions.Methods The method was validated by implementing it for the screening of NPs against different disease conditions. The biological effect of the identified NPs were evaluated based on their binding affinity with the target of their synthetic drug counterpart, prior to which, their in-silico pharmacokinetic and pharmacodynamics properties were assessed. The stability of binding was validated using molecular dynamics simulation studies.Results The study yielded NPs with significant structural similarities to synthetic drugs and binding interactions stabilizing the macromolecular structures.Conclusions The results envisage a strong indication that the natural product drugs can work in a manner similar to that of synthetic drugs if administered individually. Further, the results encourage the application of the current strategy to screen competent drugs against any disease condition ad libitum.

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Structure-based Assessment of Homologous Analogues of Natural products: A computational approach to predict the therapeutic effects of natural products

10.21203/rs.3.rs-620117/v1 ◽

2021 ◽

Author(s):

Aditya Rao ◽

Nandini Shetty

Keyword(s):

Natural Products ◽

Screening Strategy ◽

Therapeutic Effects ◽

Biological Interactions ◽

Strong Indication ◽

Disease Condition ◽

Novel Strategy ◽

Dynamics Simulations ◽

Current Screening ◽

Activity Cliffs

Abstract The present study describes a novel strategy to screen natural products (NPs) for their therapeutic effects with the predicted mechanism of action. The method entitled 'Structure-based Assessment of Homologous Analogues of Natural products-SAHANA' follows the comparison of NPs against prescribed synthetic chemical drugs to deduce activity cliffs and core fragments, based on the molecular properties and 2-dimensional structural similarities. The method was applied to predict the biological effect of the identified NPs as antidiabetic molecules. Selected NPs were assessed for their pharmacokinetic and pharmacodynamics properties. The biological interactions and structural stability of the bound structures were evaluated using molecular docking and molecular dynamics simulations. The study yielded NPs with significant structural similarities to prescribed drugs. Further, their binding interactions stabilized the macromolecular structure. The results envisage a strong indication that the natural products can produce therapeutic effects efficiently if administered individually. The results also encourage using the current screening strategy to identify competent natural product drugs against any disease condition ad libitum.

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Structure-based screening of Natural product libraries in search of potential antiviral drug-leads as first-line treatment to Covid-19 infection

10.21203/rs.3.rs-654687/v1 ◽

2021 ◽

Author(s):

Aditya Rao ◽

Nandini Shetty

Keyword(s):

Natural Product ◽

Viral Entry ◽

Antiviral Drug ◽

Therapeutic Effects ◽

Line Treatment ◽

First Line ◽

3 Dimensional ◽

Synthetic Drugs ◽

Novel Strategy ◽

First Line Treatment

Abstract The study describes a novel strategy to screen natural products (NPs) based on their structural similarities with chemical drugs and their use as first-line treatment to Covid-19 infection. In the present study, the in-house natural product libraries, consisting of a total of 26,311 structures, were screened against potential targets of 2019-nCoV/SARS-CoV-2 based on their structural similarities with the prescribed chemical drugs. The comparison was based on molecular properties, 2 and 3-dimensional structural similarities, activity cliffs, and core fragments of NPs with chemical drugs. The screened NPs were evaluated for their therapeutic effects based on predicted in-silico pharmacokinetic and pharmacodynamics properties, binding interactions with the appropriate targets, and structural stability of the bound complex. The study yielded NPs with significant structural similarities to synthetic drugs currently used to treat Covid-19 infections. The study proposes the selected NPs as Anti-retroviral protease inhibitors, RNA-dependent RNA polymerase inhibitors, and viral entry inhibitors.

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Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.13.162 ◽

2017 ◽

Vol 13 ◽

pp. 1670-1692 ◽

Cited By ~ 18

Author(s):

Santanu Hati ◽

Ulrike Holzgrabe ◽

Subhabrata Sen

Keyword(s):

Natural Products ◽

Oxidative Dehydrogenation ◽

Scientific Community ◽

Nitrogen Heterocycles ◽

Building Blocks ◽

Important Class ◽

Heteroaromatic Compounds ◽

Synthetic Drugs ◽

Convenient Approach ◽

Synthetic Drug

Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective. This review discusses various oxidative dehydrogenation strategies of C–C and C–N bonds to generate nitrogen heteroarenes from their corresponding heterocyclic substrates. The strategies are categorized under stoichiometric and catalytic usage of reagents that facilitate such transformations. The application of these strategies in the synthesis of nitrogen heteroarene natural products and synthetic drug intermediates are also discussed. We hope this review will arouse sufficient interest among the scientific community to further advance the application of oxidative dehydrogenation in the synthesis of nitrogen heteroarenes.

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Delay Stability of n-Firm Cournot Oligopolies

Mathematics ◽

10.3390/math8091615 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1615

Author(s):

Akio Matsumoto ◽

Ferenc Szidarovszky

Keyword(s):

Product Differentiation ◽

Dynamics Simulation ◽

Cyclic Behavior ◽

Simulation Studies ◽

Local Behavior ◽

Response Dynamics ◽

Stability Switches ◽

Best Response Dynamics ◽

Best Response ◽

The Stability

The dynamic behavior of n-firm oligopolies is examined without product differentiation and with linear price and cost functions. Continuous time scales are assumed with best response dynamics, in which case the equilibrium is asymptotically stable without delays. The firms are assumed to face both implementation and information delays. If the delays are equal, then the model is a single delay case, and the equilibrium is oscillatory stable if the delay is small, at the threshold stability is lost by Hopf bifurcation with cyclic behavior, and for larger delays, the trajectories show expanding cycles. In the case of the non-equal delays, the stability switching curves are constructed and the directions of stability switches are determined. In the case of growth rate dynamics, the local behavior of the trajectories is similar to that of the best response dynamics. Simulation studies verify and illustrate the theoretical findings.

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Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2020.1798813 ◽

2020 ◽

pp. 1-16 ◽

Cited By ~ 3

Author(s):

Rupesh V. Chikhale ◽

Vivek K. Gupta ◽

Gaber E. Eldesoky ◽

Saikh M. Wabaidur ◽

Shripad A. Patil ◽

...

Keyword(s):

Molecular Dynamics ◽

Natural Products ◽

Molecular Dynamics Simulation ◽

Virtual Screening ◽

Homology Modelling ◽

Dynamics Simulation ◽

Simulation Studies

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DFT, Molecular Docking and Molecular Dynamics Simulation Studies on Some Newly Introduced Natural Products for Their Potential Use Against SARS-CoV-2

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.130733 ◽

2021 ◽

pp. 130733

Author(s):

Taner Erdogan

Keyword(s):

Molecular Dynamics ◽

Natural Products ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Dynamics Simulation ◽

Simulation Studies ◽

Potential Use

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Anti-Inflammatory Properties of Plant Derived Natural Products – A Systematic Review

Current Medicinal Chemistry ◽

10.2174/0929867325666190523123357 ◽

2019 ◽

Vol 26 (24) ◽

pp. 4506-4536 ◽

Cited By ~ 4

Author(s):

Iris E. Allijn ◽

René P. Brinkhuis ◽

Gert Storm ◽

Raymond M. Schiffelers

Keyword(s):

Systematic Review ◽

Natural Products ◽

Positive Control ◽

Therapeutic Effects ◽

Reference Compound ◽

Individual Molecular Species ◽

The Past ◽

Anti Inflammatory ◽

The Individual ◽

Natural Medicines

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.

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Functional characterization and structural modelling of peptidoglycan degrading β-N-acetyl-glucosaminidase from a dental isolate of Serratia marcescens

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201103204234 ◽

2020 ◽

Vol 23 ◽

Author(s):

Aditi Rathee ◽

Anil Panwar ◽

Seema Kumari ◽

Sanjay Chhibber ◽

Ashok Kumar

Keyword(s):

Functional Characterization ◽

Major Change ◽

Crystal Form ◽

Bound State ◽

Dynamics Simulation ◽

Gram Positive ◽

Structural Cell ◽

Stability Structure ◽

Arginine Residues ◽

The Stability

Introduction:: Enzymatic degradation of peptidoglycan, a structural cell wall component of Gram-positive bacteria, has attracted considerable attention being a specific target for many known antibiotics. Methods:: Peptidoglycan hydrolases are involved in bacterial lysis through peptidoglycan degradation. β-N-acetylglucosaminidase, a peptidoglycan hydrolase, acts on O-glycosidic bonds formed by N-acetylglucosamine and N-acetyl muramic acid residues of peptidoglycan. Aim of present study was to study the action of β-N-acetylglucosaminidase, on methicillin- resistant Staphylococcus aureus (MRSA) and other Gram-negative bacteria. Results:: We investigated its dynamic behaviour using molecular dynamics simulation and observed that serine and alanine residues are involved in catalytic reaction in addition to aspartic acid, histidine, lysine and arginine residues. When simulated in its bound state, the RMSD values were found lesser than crystal form in the time stamp of 1000 picoseconds revealing its stability. Structure remained stably folded over 1000 picoseconds without undergoing any major change further confirming the stability of complex. Conclusion:: It can be concluded that enzymes belonging to this category can serve as a tool in eradicating Gram-positive pathogens and associated infections.

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