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Discovery of Therapeutic Lead Molecule Against β-Tubulin Using Computational Approach

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Abstract

Virtual screening strategy was performed against the target β-tubulin to overcome paclitaxel resistance in blood cancer types. In essence, A185T and A248V are two such important mutations frequently observed in clinical trials that confer paclitaxel resistance. In the present investigation, compounds from NPACT database were filtered by pharmacokinetics, toxicity and binding energy values. A total of 5 active compounds were identified from a list of 1574 bioactive compounds investigated in our study. Finally, we have compiled all the characteristic features into biologically meaningful clusters by hierarchical clustering algorithm. Overall, the results from our analysis indicate that glaucarubol, isolated from the bark of Ailanthus excelsa tree, could be the potential lead molecule for the treatment of paclitaxel-resistant cancer types. It is worth stressing that our result is the first such observation of inhibitory action of glaucarubol against β-tubulin and warrants further experimental investigation.

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Acknowledgements

The authors of the manuscript would like to thank the management of VIT University for providing the facility and support to carry out this research work.

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Authors and Affiliations

  1. Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India

    K. Ramanathan, Kanika Verma, Naina Gupta & V. Shanthi

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  1. K. Ramanathan
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  2. Kanika Verma
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  3. Naina Gupta
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  4. V. Shanthi
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Correspondence to K. Ramanathan.

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Ramanathan, K., Verma, K., Gupta, N. et al. Discovery of Therapeutic Lead Molecule Against β-Tubulin Using Computational Approach. Interdiscip Sci Comput Life Sci 10, 734–747 (2018). https://doi.org/10.1007/s12539-017-0233-8

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  • DOI: https://doi.org/10.1007/s12539-017-0233-8

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