Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors

Rajagopal, Kalirajan; Kulshrestha, Vivek; Sankar, S.; Selvaraj, Jubie

doi:10.1016/j.ejmech.2012.08.025

Cited by 49 publications

(30 citation statements)

References 20 publications

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“…The desired title compounds, O-benzyl-N-(9-acridinyl)hydroxylamines were prepared by reacting the prepared hydroxylamines with 9-chloroacridine 11,12 (5) as shown in Scheme 2. Initial attempts in this reaction resulted in relatively poor yields of 5, likely due to the limited availability of the free base of compounds 4.…”

Section: Resultsmentioning

confidence: 99%

O-Benzyl-N-(9-acridinyl)hydroxylamines

Johnson¹,

Duncan²,

Mosher³

2018

Arkivoc

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A series of O-benzyl-N-(9-acridinyl)hydroxylamines was prepared, isolated, and evaluated for biological activity using both thermal denaturation and MTT assays. Changes in the thermal denaturation temperature of genomic calf-thymus DNA ranged from +6.6 °C to +20.2 °C. MTT assays on SNB-19 glioblastoma cells provided biological activity that ranged from 17.4 µM to 33.2 µM. Both evaluation methods of biological activity indicate that substitution of the benzyl group by either electron-withdrawing or electron-donating groups provides a measureable benefit in these assays. The two assays agreed on the magnitude of the interaction for each substitution pattern.

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Section: Resultsmentioning

confidence: 99%

O-Benzyl-N-(9-acridinyl)hydroxylamines

Johnson¹,

Duncan²,

Mosher³

2018

Arkivoc

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“…Glide generates conformations internally and passes these through a series of filters. The final energy evaluation is done with Glide Score and a single best pose is generated as the output for a particular ligand (Kalirajan et al, 2012). Most of drug candidates fail in clinical trials due to poor ADME properties.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Design, synthesis and antidepressant activities of some novel fatty acid analogues

et al. 2014

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The present study deals with the optimization of some novel heterocyclic compounds containing two biological scaffolds such as long alkyl/alkenyl side chain of fatty acids and five-membered azoles named as 1,3,4-oxadiazole, 1,2,4-triazole and 1,3,4-thiadiazoles as antidepressant agents. In-silico docking studies have been carried out for the tested compounds into the crystal structure of human mono amine oxidase-B using GLIDE integrated Maestro (9.3) version. Five analogues exhibited higher XP G-Scores than selegeline. Also, it was verified by in vivo antidepressant screening, where two of the compounds PA-2 and GLA-2 showed significant antidepressant activity. Drug likelinesss and comparative bioactive analysis for the analogues are done using Qik.Prop 3.4.

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“…Similarly oxazine derivatives also have various biological activities 13,14 like antimicrobial, anticancer etc. In continuous of our previous research work, [15][16][17][18] on searching new potent cytotoxic agents, we have designed 9-anilinoacridine analogues bearing the oxazine residue on anilino rings for topoisomerase II inhibition by molecular docking studies by using by using Schrodinger suit-2012 Maestro 9.3 version. The results revealed that the newly designed 9-anilinoacridine analogues derivatives exhibited good inhibition with topo II.…”

Section: Introductionmentioning

confidence: 99%

“…A good example of such a compound is amsacrine a well known antiproliferative agent used to treat some types of cancers including acute adult leukemia. 16 The crystal structure of protein Human Topoisomerase IIa (PDB ID: 1ZXM) at 1.87A o was downloaded from the Protein Data Bank (PDB) and was used in order to model the protein structure in this study. In general, the protein structures are refined for their bond orders, formal charges and missing hydrogen atoms, topologies, incomplete and terminal amide groups.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors

Rajagopal¹,

Sankar²,

Selvaraj³

et al. 2017

IJPER

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Introduction:In general, 9-aminoacridine derivatives are inhibiting DNA topoisomerase II (topoII) because of their strong activity due to the ability of acridine nucleus to intercalate into DNA base pair. To get insight of the intermolecular interactions, the molecular docking studies are performed at active site of topoisomerase II. Aim: In this study, an attempt is made for identification of potential ligands from oxazine substituted 9-anilino acridines targeted against topoisomerase-II (1ZXM) using molecular modelling and docking studies by using Schrodinger suit-2012 Maestro 9.3 version. Insilco ADMET screening also performed by qikprop module of Schrodinger suit. Results: The relative binding affinity of the designed compounds towards topoisomerase-II (1ZXM) was selected on the basis of docking score, GLIDE score and interaction patterns. Several compounds showed strong hydrogen bonding interactions with amino acid residues and their hydrophobic interactions and other parameters could also explain their potency to inhibit topoisomerase-II (1ZXM). The oxazine substituted 9-anilino acridine derivatives 1a-1k have good binding affinity with Glide score in the range of -5.7 to -8.06 when compared with the standard ledacrine (-5.24). The ADMET screening of the designed compounds have almost all the properties of the compounds are within the recommended values. Conclusion: Hence, this study provides evidence for consideration of valuable ligands in oxazine substituted 9-anilino acridine derivatives as potential topoisomerase-II inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential

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Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors

Cited by 49 publications

References 20 publications

O-Benzyl-N-(9-acridinyl)hydroxylamines

O-Benzyl-N-(9-acridinyl)hydroxylamines

Design, synthesis and antidepressant activities of some novel fatty acid analogues

Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors

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