Targeting galectin-3 by natural glycosides: a computational approach

Arifuzzaman, Md.; Hamza, Amir; Zannat, Syeda Sakiatuz; Fahad, Rubaiyat; Rahman, Azizur; Hosen, S. M. Zahid; Dash, Raju; Hossain, Md. Kamrul

doi:10.1007/s13721-020-0219-z

Cited by 10 publications

(6 citation statements)

References 99 publications

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“…The PDB ID used for CDK2 protein kinase was 2BHY. Proteins and compounds were prepared for docking by using an established procedure [ 68 ]. Discovery Studio was used for making 2D interaction figures.…”

Section: Methodsmentioning

confidence: 99%

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

et al. 2020

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Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.

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Section: Methodsmentioning

confidence: 99%

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

et al. 2020

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“…MD simulation is an imperative method to explore the protein-ligand complex in real-time, widely used to assess the conformational variability and stability of the protein systems (Mahmud et al, 2020;Bappy et al, 2020;Islam et al, 2019). The molecular dynamics simulation represents stable RMSD compared to ligand free apo structure and control which provides insights about the structural integrity of the docked complex (Dash et al, 2019;Arifuzzaman et al, 2020). Furthermore, Rg pro le was illustrated along with RMSD pro le, where RMSD describes the uctuation during simulation periods, and protein folding and degree of compactness describes through Rg.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics approaches to investigate the phytochemicals of Centella asiatica against the main protease of SARS-CoV-2

Khan¹,

Khan²,

Rahman³

et al. 2021

Preprint

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The recent pandemic caused by the novel coronavirus SARS-CoV-2 has impacted global health by increasing mortality and unexpected infection rate. Extensive clinical research is undergoing to repurposing the old drug against this virus. So, this is an emerging need to develop therapy against the virus. Plant-derived natural products have proven to be potent therapeutics for several infections and diseases. Centella asiatica, is a native plant of the Indian subcontinent, has been vastly using as folk medicine against diseases including infectious diseases. So, using bioinformatics approach we identified and checked the phytochemicals of the plant as inhibitors against the main protease (Mpro), the key regulatory enzyme of the SARS-CoV-2 lifecycle. Computer-aided drug designing methods were performed to reveal the best nine drug-like phytochemicals those theoretically have the higher binding affinity of inhibiting Mpro. This outcome may direct to the development of potent therapeutics against the SARS-CoV-2 and demands experimental validation.

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“…The PDB IDs used for the isoforms were 2HI4, 3E4E, 4GQS, 2F9Q, and 1W0G for CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A4, respectively. Proteins and ligands were prepared for docking by the established procedure [ 37 ]. Structural alignment of apo and galeon bound states of CYP3A4 was performed using Pymol.…”

Section: Methodsmentioning

confidence: 99%

“…The DEREK software was utilized to screen for structural alerts to confirm our bio-activation proposal and predicted toxicity of galeon metabolites. In order to identify the binding mechanism of galeon with all CYP450 isoforms, molecular docking was carried out using a previously reported method [37]. The protein structures of the corresponding CYP450 isoforms were downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) database (https://www.rcsb.org/) in PDB format.…”

Section: In Silico Studymentioning

confidence: 99%

“…Thirdly, we report on galeon's metabolic profile through in vitro metabolic experiments using rat liver microsomes (RLMs) in which identification of possible metabolites and confirmation of their structures were carried out using Ion-trap tandem mass spectrometry (LC-MS/MS). Finally, we conducted molecular docking analysis [37] in order to identify the binding mechanism of galeon with all CYP450 isoforms. reported to have potent biological activities, their further development is hampered due to the fact of their poor bioavailability and toxicity (i.e., generation of toxic reactive metabolites).…”

Section: Introductionmentioning

confidence: 99%

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Galeon: A Biologically Active Molecule with In Silico Metabolite Prediction, In Vitro Metabolic Profiling in Rat Liver Microsomes, and In Silico Binding Mechanisms with CYP450 Isoforms

et al. 2020

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Galeon, a natural cyclic-diarylheptanoid (CDH), which was first isolated from Myrica gale L., is known to have potent cytotoxicity against A549 cell lines, anti-tubercular activity against Mycobacterium tuberculosis H37Rv, chemo-preventive potential, and moderate topoisomerase inhibitory activity. Here, in silico metabolism and toxicity prediction of galeon by CYP450, in vitro metabolic profiling study in rat liver microsomes (RLMs), and molecular interactions of galeon-CYP450 isoforms were performed. An in silico metabolic prediction study showed demethyl and mono-hydroxy galeon were the metabolites with the highest predictability. Among the predicted metabolites, mono-hydroxy galeon was found to have plausible toxicities such as skin sensitization, thyroid toxicity, chromosome damage, and carcinogenicity. An in vitro metabolism study of galeon, incubated in RLMs, revealed eighteen Phase-I metabolites, nine methoxylamine, and three glutathione conjugates. Identification of possible metabolites and confirmation of their structures were carried out using ion-trap tandem mass spectrometry. In silico docking analysis of galeon demonstrated significant interactions with active site residues of almost all CYP450 isoforms.

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Targeting galectin-3 by natural glycosides: a computational approach

Cited by 10 publications

References 99 publications

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

Bioinformatics approaches to investigate the phytochemicals of Centella asiatica against the main protease of SARS-CoV-2

Galeon: A Biologically Active Molecule with In Silico Metabolite Prediction, In Vitro Metabolic Profiling in Rat Liver Microsomes, and In Silico Binding Mechanisms with CYP450 Isoforms

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