Exploring β‐Tubulin Inhibitors from Plant Origin using Computational Approach

Verma, Kanika; Kannan, Kaavya; Shanthi,; Sethumadhavan, Rao; Karthick,; Ramanathan, K.

doi:10.1002/pca.2665

Cited by 16 publications

(17 citation statements)

References 70 publications

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“…Thus, computer aided drug designing and analysis can provide an insight into various unknown mechanisms (Karuppasamy et al, 2017;Purohit & Sethumadhavan, 2009). Docking and molecular dynamic studies are proved to be excellent tools in designing new drugs (Verma et al, 2017). In the case of COVID-19, many studies have provided a blueprint about the structure of the virus.…”

Section: Introductionmentioning

confidence: 99%

Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings

Avti

Chauhan

Shekhar

et al. 2021

Journal of Biomolecular Structure and Dynamics

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The coronavirus disease 2019 (COVID-19) pandemic is caused by newly discovered severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). One of the striking targets amongst all the proteins in coronavirus is the main protease (M pro ), as it plays vital biological roles in replication and maturation of the virus, and hence the potential target. The aim of this study is to repurpose the Food and Drug Administration (FDA) approved molecules via computer-aided drug designing against M pro (PDB ID: 6Y2F) of SARS CoV-2 due to its high x-ray resolution of 1.95 Å as compared to other published M pro structures. High Through Virtual Screening (HTVS) of 2456 FDA approved drugs using structurebased docking were analyzed. Molecular Dynamics simulations were performed to check the overall structural stability (RMSD), Ca fluctuations (RMSF) and protein-ligand interactions. Further, trajectory analysis was performed to assess the binding quality by exploiting the protein-residue motion cross correlation (DCCM) and binding free energy (MM/GBSA). Tenofovir, an antiretroviral for HIV-proteases and Terlipressin, a vasoconstrictor show stable RMSD, RMSF, better MM/GBSA with good cross correlation as compared to the Apo and O6K. Moreover, the results show concurrence with Nelfinavir, Lopinavir and Ritonavir which have shown significant inhibition in in vitro studies. Therefore, we conclude that Tenofovir and Terlipresssin might also show protease inhibition but are still open to clinical validation in case of SARS-CoV 2 treatment.

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Section: Introductionmentioning

confidence: 99%

Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings

Avti

Chauhan

Shekhar

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…The ProTox calculation is based on 2D similarity to molecules exhibiting known LD50 values and on the recognition of chemical fragments that were overrepresented in compounds found to be toxic [46]. According to the Globally Harmonised System (GHS), toxicity is categorized into the six different classes based on LD50 range [47] published by the Occupational Safety and Health Administration (OSHA) [48] (Supporting Information Table S2).…”

Section: Admet Analysismentioning

confidence: 99%

“…The toxicity features (mutagenicity, tumorigenicity, irritant and reproductive effect) of the compounds were estimated based on the precompiled lists of fragments available using the Brazilian Archives of Biology and Technology. Vol.64: e21200402, 2021 www.scielo.br/babt algorithm that gives rise in the toxicity alerts in case that the compound structure is similar to that of the list of toxic fragments [48].…”

Section: Toxicity Feature Valuationmentioning

confidence: 99%

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

Verma

Mahalapbutr

Suriya

et al. 2021

Braz. arch. biol. technol.

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Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using HIGHLIGHTS  Flavonoids potentially target GyrB. Screened flavonoids have good bioavailability and no toxicity.

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“…This drug interacts with the β-subunit of polymerised microtubules and prevents their depolymerisation, which, in turn, results in mitotic arrest and apoptosis. Verma et al (66) tried to identify a potent β-tubulin inhibitor using experimental and in silico approaches. For this purpose, compounds were extracted from Cassia fistula and their structure identified by GC-MS.…”

Section: Natural Compoundsmentioning

confidence: 99%

“…Searching the Naturally Occurring Plant-based Anticancer Compound-Activity-Target (NPACT) database, Verma et al (66) identified 1574 alkaloids with anticancer potential. Their pharmacokinetics and toxicity, binding efficiency, binding affinity of the docked complex, and metabolising capacity were evaluated by several computer programs.…”

Section: Natural Compoundsmentioning

confidence: 99%

An overview of microtubule targeting agents for cancer therapy

Karahalıl

Yardım-Akaydin

Baytas

2019

Archives of Industrial Hygiene and Toxicology

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The entire world is looking for effective cancer therapies whose benefits would outweigh their toxicity. One way to reduce resistance to chemotherapy and its adverse effects is the so called targeted therapy, which targets specific molecules (“molecular targets”) that play a critical role in cancer growth, progression, and metastasis. One such specific target are microtubules. In this review we address the current knowledge about microtubule-targeting agents or drugs (MTAs/MTDs) used in cancer therapy from their synthesis to toxicities. Synthetic and natural MTAs exhibit antitumor activity, and preclinical and clinical studies have shown that their anticancer effectiveness is higher than that of traditional drug therapies. Furthermore, MTAs involve a lower risk of adverse effects such as neurotoxicity and haemotoxicity. Several new generation MTAs are currently being evaluated for clinical use. This review brings updated information on the benefits of MTAs, therapeutic approaches, advantages, and challenges in their research.

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Exploring β‐Tubulin Inhibitors from Plant Origin using Computational Approach

Abstract: This is the first observation of inhibitory activity of isostrychnine against β-tubulin and warrants further experimental investigation. Copyright © 2016 John Wiley & Sons, Ltd.

Cited by 16 publications

References 70 publications

Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings

Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

An overview of microtubule targeting agents for cancer therapy

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