QSAR STUDIES OF SAPONINE ANALOGUES FOR ANTICANCER

ACTIVITY

GUIDE- Dr. S. L. DEORE.

PRESENTED BY – Mr. SAGAR S. ALONE.

SUMMARY

Introduction

Review of Literature

Aim & Objective

Need & Scope

Plan of Work

References2Government College Of Pharmacy, Amravati.

INTRODUCTION [1]

To build the mathematical relationship between the chemical structure and Biological activity.

Physicochemical properties or structures are expressed by numbers.

One can form a mathematical relationship, or quantitative structure-activity relationship between the two.

The mathematical expression can then be used to predict the biological response of other chemical structures.

Activity = ƒ (Physicochemical properties and /or structural properties)

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Summary of biological and chemical properties explored in QSAR studies [1]

Biological properties

1) Bioconcentration2) Biodegradation3) Carcinogenicity4) Drug metabolism

and clearance 5) Inhibitor constant6) Mutagenicity7) Permeability8) Blood brain barrier9) Skin10) Pharmacokinetics11) Receptor binding

Chemical properties

1) Boiling point2) Chromatographic retention time3) Dielectric constant4) Diffusion coefficient5) Dissociation constant6) Melting point7) Reactivity 8) Solubility 9) Stability 10) Thermodynamic properties 11) Viscosity

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CANCER [3]

Carcinogens can be present in food ,water, air, in chemicals and sunlight that people are exposed to.

In 1996 there were 10 million new cancer cases worldwide and six million deaths attributed to cancer.

In 2020 there are predicted to be 20 million new cases and 12 million deaths.

A globalization of unhealthy lifestyles, particularly cigarette smoking and the adoption of many features of the modern Western diet (high fat, low fibre content) will increase cancer incidence.

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SAPONIN Soap-like foaming when shaken in aqueous solutions [4]. two kinds of saponins are recognized – the steroidal and the pentacyclic

triterpenoid types [5]. More than half of terrestrial plants may contain saponins. Diversified pharmacological effects (haemolytic, cytotoxic, antitumor, anti-

inflammatory, molluscicidal [9]. Saponins have been shown to induce both cycle arrest and apoptosis within

cancerous cells [10]. Isolation of saponins from plant extracts is often a long and fastidious

process involving many purification steps and usually only small amounts

of products are obtained in a pure and homogeneous form [11]. Therefore, chemical synthesis of saponin analogue appear to be a rational

way to gain access to adequate amounts of saponins in order to promote

further pharmaceutical studies [12].6Government College Of Pharmacy, Amravati.

O

O

OH

H

O

HOO

OHO

HO OH OH

O

HO

O

OH

HOOH

Advantages of QSAR [2]

Quantifying the relationship between structure and activity.

Activity provides an understanding of the effect of structure on activity.

Potential to make predictions leading to the synthesis of novel analogues.

Help to understand interactions between functional groups in the molecules of greatest activity, with those of their target.

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Applications of QSAR [2]

Modern drug design & drug discovery.

Prediction of biological activity.

Study of different physicochemical properties affecting biological activity.

Prediction of Chemical toxicity.

To study Mechanism of action.

Prediction of molecular properties.

ADME properties prediction. 8Government College Of Pharmacy, Amravati.

REVIEW OF LITERATURE

Siddiqi Mohammad Imran,CDRI Lucknow have presented a paper which included following aspects of molecular modeling containing, a technique for the investigation of molecular structures and Activities/properties using computational chemistry & biology and graphical visualization techniques in order to provide a plausible 3-D representation [16].

Bang Seong-Cheol, et al, (2005) have done antitumor Activity of Pulsatilla koreana Saponins and Their Structure–Activity Relationship he mentioned Seventeen saponins isolated from the root of Pulsatilla koreana were examined for their in vitro cytotoxic activity against the human solid cancer cell lines [17].

Yan L. L et al. (2009) have done invitro and in vivo anticancer activity of steroid saponins of Paris Polyphylla Var. Yunnanensis, to confirm the anticancer activity of steroid saponins isolated from the rhizome of Paris polyphylla var. yunnanensis and evaluate the structure-activity relationships of these steroid saponins in vitro and in vivo [18].

Malik Adeel et al. (2006) have presented review article Databases and QSAR for Cancer Research in this review, he take a survey of bioinformatics databases and quantitative structure-activity relationship studies reported in published literature [19].

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CONT….

Gauthier Charles et al. (2009) have investigated recent Progress in the Synthesis of Naturally Occurring Triterpenoid Saponins and describe recently reported semi- and total syntheses of naturally occurring triterpenoid saponins [20].

Matthew J. et al, (2009) have done Structural analogues of diosgenyl saponins synthesis and anticancer activity and he studied Saponins display various biological activities including anti-tumor activity [21].

Chanin Nantasenamat et al (2009) has presented review article a practical overview of quantitative structure-activity relationship in this review article author describes history and development of QSAR model and study QSAR modeling pertains to the construction of predictive models of biological activities as a function of structural and molecular information of a compound library [1].

Dholwani K. K et al (2008) have presented a review article on plant derived natural product and their analogue with antitumor activity” and describes traditional medicine including Chinese herbal formulation can serve as a potential new drugs and initial research focus on the isolation of bioactive lead compounds [22].

Tsubuki Masayoshi et al. (2008) has done a new synthesis of potent antitumor saponin OSW-1 Via Witting rearrangement and he work on OSW-1 and its analogues [23].

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AIM AND OBJECTIVE

To study the different physicochemical parameter(Descriptors) affecting anticancer activity.

To elaborate the role of saponins analogues in anticancer activity.

To obtain the relationship between different physicochemical parameter and the biological activity of saponin analogues.

To increase the database of saponin analogues for anticancer activity.

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NEED AND SCOPE

Medical oncology is an important frontier which has gained attention from various research communities.

The mortality rate of cancer patients is usually high (65%).

Primarily there are three treatment methods for cancer: [24] (a) Invasive methods - Surgical removal of cancer tissue. (b) Irradiation methods - Use of high energy radiation. (c) Chemotherapy - Administration of toxic drugs.

To control cancer from mankind we should discover or make new compound by using QSAR before going work into actual wet laboratory.

QSAR techniques will continue to make a valuable contribution to the computer-assisted analysis of structure-bioactivity relationships.

Hence taking into consideration the part of present research which we are performing to do QSAR study of different saponin analogues having anticancer activity by using Modern computational technology (QSAR).

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PLAN OF WORK

1) Literature survey.

2) Selection of saponin analogues for anticancer activity.

3) Study of descriptors.

4) Design and making structure of saponin analogues.

5) QSAR studies.

6) Result and Discussion.

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REFERENCES

[1] Chanin Nantasenamat et.al. (2009) A practical overview of quantitative structure-activity relationship, excli Journal, pp.74-88.

[2] Tatsuhiko Yoshino, (2010) QSAR in Catalysis in Silico Catalyst Design, pp.1-15.

[3] Alison Malcolm R, (2001) Cancer. Encyclopedia of life sciences, Nature Publishing Group, pp.1-8.

[4] Hostettmann, K et.al. (1995). Saponins. Cambridge: Cambridge University Press. Pp.32970-71.

[5] Osbourn, A. (1996) Saponins and plant defence – a soap story. Trends Plant Sci. vol 1, pp 4-9.

[6] Vincken, J. P.et.al. (2007) Saponins, classification. And occurrence in the plant kingdom. Phytochemistry, 68, pp.275 297.  [7] Agrawal, P. K et.al. (1985) Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins. Phytochemistry, pp.2479-2496.  [8] Agrawal, P. K. et.al. (1992) NMR spectroscopy of oleanane triterpenoids. Prog. Nucl. Mag, pp.1-90.

[9] Agrawal, P. K et.al. (1996) Nuclear magnetic resonance spectroscopic approaches for the determination of interglycosidic linkage and sequence in oligosaccharides. Phytochem. Anal.7, pp.113-130.  [10] Sahu N. P et.al. (2001) Advances in structural determination of saponins and terpenoid glycosides. Curr. Org. Chem 5, pp.315- 334.

[11] Qin, G. W et.al. (1998) Some progress on chemical studies of triterpenoid saponins from Chinese medicinal plants. Curr. Org. Chem 2, pp.613-625.  [12] Liu, J.et.al. (2002) Traditional Chinese medicine (TCM): Are polyphenols and saponins the key ingredients triggering biological activities? Curr Med. Chem 9, pp.1483-1485. 

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REFERENCES

[13] Riguera, Ricardo, (1997). Isolating bioactive compounds from marine organisms Journal of Marine Biotechnology 5 (4) pp.187–193.

[14] Liener, Irvin E (1980). Toxic constituents from plant foodstuffs. New York City: Academic Press. p.161.

[15] Francis, George et.al. (2002). The biological action of saponins in animal Systems: a review. British Journal of Nutrition 88 (6): pp.587–605.

[16] Mohammad Imran Siddiqi, (2007) QSAR: Principles and Selected Case Studies, CDRI, Lucknow.

[17] Seong-Cheol Bang, et al (2005) Antitumor Activity of Pulsatilla koreana Saponins and Their Structure–Activity Relationship Chem. Pharm. Bull, pp.1451—1454.

[18] L.L. Yan, et al (2009) In vitro and in vivo anticancer activity of steroid saponins of Paris Polyphylla var. Yunnanensis Exp Oncol pp.27–32.

[19] Malik Adeel, Singh Hemajit, et al. (2006) Databases and QSAR for cancer research cancer informatics, Cancer Inform 2: pp.99–111.

[20] Charles Gauthier et.al. (2009) Recent Progress in the Synthesis of Naturally Occurring Triterpenoid Saponins, Mini-Reviews in Organic Chemistry vol-6, pp.321-344.

[21] Kaskiw M. J et al, (2009) Structural analogues of diosgenyl saponins: Synthesis and anticancer activity, Bioorg. Med. Chem pp.7670–7679.

[22] Dholwani K.K., et al, (2008) A review on plant derived natural product and their analogue with antitumor activity, Indian J pharmacol Apr, issue 2, pp.49-58.

[23] Masayoshi Tsubuki et. al. (2008) A new synthesis of potent antitumor saponin OSW-1Via Wittig rearrangement Tetrahedron, pp.229–232.

[24] Paila, Hari Srinivas Kalyan, (2008) M.S. Molecular Modeling Studies of Curcumin Analogs as Anti-Angiogenic Agents pp.97.

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Government College Of Pharmacy, Amravati. 16THANK YOU