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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

In Silico designing of Potential Noscapine Analogue and Pharmacological Evaluation using Chemoinformatics approach

Noscapine and its derivatives have been explored for its interaction with tubulin protein, to be used as strong anticancer agent. A detailed computational analysis have been performed to determine the noscapine analog to inhibit the tubulin protein with high specificity, overcoming the issues of non-specificity and side effects associated with potential interaction. In this study, noscapine analogs were designed using the state of art methodology employing alkyl groups, in order to enhance the potency of the drug to bind target tubulin receptor (potential target for cancer treatment). We have performed the molecular docking and molecular dynamics simulation. Also, pharmacological evaluations were also performed to assess the pharmacokinetic properties of the lead compound. Our results illustrated that compound-1 posses the strongest interaction with the target tubulin protein with higher binding free energy score of -8.49 kcal/mol among the whole library and noscapine (-7.86 kcal/mol). Our results were confirmed by the molecular dynamics simulation study of lead compound tubulin complex with lower RMSD and atomic fluctuation values. Importantly, lead compound was found to good pharmacokinetic properties and showed the potential lead to be used as potential cancer therapeutics.

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References
    C. Conde, A. Cáceres. (2009). Microtubule assembly, organization and dynamics in axons and dendrites. Nature Rev, Neurosci. 10(5), 319-332.

    P.K. Naik, M. Lopus, R. Aneja, S.N. Vangapandu, H.C.Joshi (2012). In silico inspired design and synthesis of a novel tubulin-binding anti-cancer drug: folate conjugated noscapine (Targetin), J. Comput. Aided Mol. Des. 26(2), 233-247.

    Y.Lu, J.Chen, M. Xiao, W. Li, D.D.Miller (2012). An overview of tubulin inhibitors that interact with the colchicine binding site, Pharm. Res. 29(11), 2943-2971.

Vartika Tomar
Neeraj Kumar
Ramesh Chandra

Drug Discovery & Development Laboratory
Department of Chemistry
University of Delhi
Delhi-110007, India

E-mail: acbrdu@hotmail.com