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OJBTM

Online Journal of Bioinformatics©

Volume 21(2): 132-146, 2020.


Screening for taxanes with β tubulin inhibition and multidrug resistance.

 

Naga Vignesh Selvaraj, Kandavel Palani Kannan and Gopal Ramesh Kumar.

 

Bioinformatics Lab, AU-KBC Research Centre, MIT Campus of Anna University, Anna University Chennai,  Chennai -600044, India.

 

ABSTRACT

 

Selvaraj NV, Kannan KP, Kumar GR., Screening for taxanes with β tubulin inhibition and multidrug resistance, Onl J Bioinformatics., 21(2): 132-146, 2020. Screening for taxanes with β tubulin inhibition and multidrug resistance (MDR) is described. Seventy two natural β tubulin inhibitors were found within 260 natural taxanes at Taxane Knowledge Base (Tax KB) by drug design (CADD) and virtual screening with docking simulation. Criteria for activity was ligand solvation in binding free energy function. We found 5 natural taxanes with potent microtubule inhibition less than μM’s. Prediction of activity spectra confirmed that 2alpha, 9alpha-Dihydroxy-10beta, 13alpha-Diacetoxy-5alpha-cinnamate taxa-4(20), 11-diene and 2alpha, 10beta-Dihydroxy-9alpha, 13alpha-Diacetoxy-5alpha-cinnamate taxa-4 (20), 11-diene) could exhibit most potent microtubule inhibition. Physicochemical logP, rotatable and hydrogen bond donors and acceptors in these taxanes may enhance passive transcellular transport compared to current MDR modulators.

 

Keywords: Taxanes, β tubulin, Multi Drug Resistance (MDR), Taxane Knowledge Base (Tax KB), Virtual screening, Docking.


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