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A Biophysical Approach To Identify Active Sites Of Isolated Pure Herbal Compounds And Cell Signaling In Cancers

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Title A Biophysical Approach To Identify Active Sites Of Isolated Pure Herbal Compounds And Cell Signaling In Cancers
 
Creator Samanta, Suman Kumar
 
Subject Infectious Diseases and Immunology
 
Description Natural compounds have exerts promising outcomes in cancer therapy for decades.
These compounds provided several leads molecule, which are subsequently used in the
blueprint of drug development in cancer treatment. For the search of lead compounds, we have
selected a few medicinal plants from the various parts of our country. Barringtonia Racemosa
has been used as traditional medicine for the treatment of various diseases. Anti-tumor
property of the seed extract in mice model prompted us to search for the active component
present in fruit extract. Quercetin 3-O-rutinoside (QOR) was isolated from the fruits of this
plant and quantified by HPLC method. The compound was identified by IR, Mass, NMR (1D, 2D)
spectral data analysis. QOR showed dose and time dependent anti-proliferative activity in
several leukemic cell lines with negligible effect on normal human PBMC.
Additionally, another Indian medicinal plant, curcuma caesia was selected for the
identification of the active compound present in the plant material. Bio-active guided
fractionation helped us in identification of an active compound present as (1s, 4s, 5s, 10R)-
Zedoarondiol in the root extract. It showed cytotoxicity against different cancer cell lines.
Next, Mahanine isolated from Murraya Koengii has been established as a potent anticancer
molecule against different cancer including NSCLC. Even at early dose, mahanine
inhibited phosphorylation of mTOR and also the total protein effectively in lower dose and as
consequent events, inhibition of p70S6K and AKT were observed in NSCLC. To identify the
active functional groups of mahanine responsible for biological activity, structure-activity
relation was determined. Accordingly, -OH at C-7 and -NH were chemically modified. The
concentration dependent anti-proliferative activity of mahanine and its four derivatives in an
array of nineteen different cell lines from seven different types of cancers revealed that both C-
7-OH and NH groups are active functional groups responsible for its biological activity. Using
several biophysical techniques we established that complexation of mahanine with DNA is
minor groove bound conformation with high binding efficacy. These findings will help to design
potent anti-cancer agent, which may be helpful for the development of target specific efficient
drug.
 
Date 2013
 
Type Thesis
NonPeerReviewed
 
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Identifier http://www.eprints.iicb.res.in/2009/1/Acknowledgement%2C2.pdf
http://www.eprints.iicb.res.in/2009/2/Appendix_I_Abbreviations%2C11.pdf
http://www.eprints.iicb.res.in/2009/3/Appendix_II_Presentations%2C12.pdf
http://www.eprints.iicb.res.in/2009/4/Appendix_III_Publications%2C13.pdf
http://www.eprints.iicb.res.in/2009/5/Appendix_IV_Reprints%2C14.pdf
http://www.eprints.iicb.res.in/2009/6/Chaper_2%2C6.pdf
http://www.eprints.iicb.res.in/2009/7/chapter_1%2C5.pdf
http://www.eprints.iicb.res.in/2009/8/Chapter_3%2C7.pdf
http://www.eprints.iicb.res.in/2009/9/Chapter_4%2C8.pdf
http://www.eprints.iicb.res.in/2009/10/Chapter_5%2C9.pdf
http://www.eprints.iicb.res.in/2009/11/Chapter_6%2C10.pdf
http://www.eprints.iicb.res.in/2009/12/CONTENT%2C3.pdf
http://www.eprints.iicb.res.in/2009/13/Front_page%2C1.pdf
http://www.eprints.iicb.res.in/2009/14/merged_document%2CReprints%2C15.pdf
http://www.eprints.iicb.res.in/2009/15/synopsis%2C4.pdf
Samanta, Suman Kumar (2013) A Biophysical Approach To Identify Active Sites Of Isolated Pure Herbal Compounds And Cell Signaling In Cancers. PhD thesis, University of Calcutta.
 
Relation http://www.eprints.iicb.res.in/2009/