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

Abstract

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