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image of In silico Study of Novel Tryptanthrin-Based Topoisomerase Inhibitors

Abstract

Background

Over the past ten years, a remarkable number of changes have occurred in the field of cancer drug research. Most anticancer drugs from the first generation work by breaking down DNA, preventing its production, interfering with cell division processes, or attaching to microtubules. The potential use of tryptanthrin as well as its analogues is well documented for anticancer properties.

Objective

To design a novel hybrid of tryptanthrin analogs with expected anticancer activity.

Method

By changing the C-6 carbonyl position of the tryptanthrin molecule, a set of 72 derivatives of substituted-6-benzylidine-6-indolo[2,1-] quinazoline-12-one was developed. These ligands were screened using Schrodinger Glide extra precision docking against DNA topoisomerase using doxorubicin and teniposide as references to identify their potential anticancer properties. Further, these ligands were subjected to an ADMET study to identify their drug likeliness.

Results

Combined results of molecular docking and ADMET study suggest that out of the total 72 ligands, 6 ligands RC 51, RC 29, RC 42, RC 3, RC 54, and RC 63 were showing very better binding affinity than the natural ligand adenylyl-imidodiphosphate and the two standard reference drugs- doxorubicin and teniposide.

Conclusion

Our computational approach was successful in identifying ligands that are potentially potent topoisomerase inhibitors. These can be tested further using and analysis.

© 2024 Bentham Science Publishers
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2024-10-24
2025-01-09

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/content/journals/mc/10.2174/0115734064334604241014024205
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In silico Study of Novel Tryptanthrin-Based Topoisomerase Inhibitors
Bentham Science Publishers ; https://doi.org/10.2174/0115734064334604241014024205
/content/journals/mc/10.2174/0115734064334604241014024205
/content/journals/mc/10.2174/0115734064334604241014024205
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  • Article Type:     Research Article
Keywords: Topoisomerase IIα ; Antitumor ; Tryptanthrin ; ATPase domain ; Pharmacokinetics ; Molinspiration ; Glide Extra Precision docking

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