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Albany 2019: 20th Conversation - Abstracts

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

A fluoroamine derivative of epigallocatechin gallate exhibits both, anti-cancer and anti-tuberculosis properties. Insights from in silico and in vitro studies

Epigallocatechin gallate (EGCG), has been reported to have both anti-cancer and anti- mycobacterial properties. Fluorinated compounds are known to inhibit both TB and cancer (Hoagland et al.2016). Few derivatives of EGCG were drawn structurally and subsequently chemically synthesized. A derivative with a fluorine and amine moiety was analyzed for inhibitory properties against (M. tb) and cancer using in silico), and in vitro approaches. In silico approach included docking of the optimized ligand to the enoyl reductase (ER) receptor of M. tb using AutoDock (v 4.0) and Hex. Molecular Dynamic (MD) simulation of this docked receptor-ligand complex using Gromacs (v.4.2) was then conducted. Fluoroamine derivative of EGCG inhibited Mycobacterium smegmatis, in silico (dock energy -10.9 kcal mol-1), in vitro and also inhibited the tyrosine kinase (TK) receptor Her2 and taxanes (TXL) microtubule receptor of cancer cells. The fluoroamine derivative also showed better inhibition of Mycobacterium smegmatis than EGCG based on these studies. Further, MD simulation of the fluoroamine derivative substantiated the docking results, since the receptor ligand complex showed greater stability than the receptor protein after 50 ns of MD simulation as evidenced from the RMSD, RMSF and energy profiles (Potential Energy, Kinetic Energy and Total Energy) in line with observations of Gholami and Bordbar (2017). The anti-cancer properties of the fluoroamine derivative evaluated in vitro in the Jurkat human leukemia cell line, showed almost a tenfold better inhibition than EGCG as reported in the literature. Taken together, these findings hold much promise for further study of the anti- TB and anti- cancer properties of the fluoroamine derivative.

References
    Hoagland, D.T., Liu, J., Lee, R.B., and Lee, R.E. (2016).New agents for the treatment of drug resistant Mycobacterium tuberculosis.Advanced drug delivery reviews.102:55-72.

    Gholami, S. and Bordbar, A.K. (2017).Putative binding sites of dopamine and arachidonoyl dopamine to beta lactoglobulin: A molecular docking and molecular dynamics study. Phys. Chem. Res., 5:2: 205-219.

Samarendra Narayanan,
K. V. Ramesh, and
Dipti Mothay

School of Sciences,
Jain University,
Jayanagar,
Bangalore 560011, India

sam19narayan@yahoo.co.in *
kv.ramesh@jainuniversity.ac.in