This document discusses quantitative structure-activity relationship (QSAR) modeling for predicting the anticancer activity of saponin analogues. It provides background on QSAR and lists biological properties and chemical descriptors that may be relevant for modeling. The objectives are to study relationships between physicochemical parameters and biological activity of saponin analogues to increase the database for anticancer activity prediction. The proposed work plan includes literature review, selecting analogues, studying descriptors, designing structures, QSAR studies and reporting results. Relevant references on QSAR applications, saponin synthesis and biological activities are also cited.

1. GUIDE- Dr. S. L. DEORE.
PRESENTED BY – Mr. SAGAR S. ALONE.

2.  Introduction
 Review of Literature
 Aim & Objective
 Need & Scope
 Plan of Work
 References
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3.  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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4.  Biological properties
1) Bioconcentration
2) Biodegradation
3) Carcinogenicity
4) Drug metabolism and
clearance
5) Inhibitor constant
6) Mutagenicity
7) Permeability
8) Blood brain barrier
9) Skin
10) Pharmacokinetics
11) Receptor binding
 Chemical properties
1) Boiling point
2) Chromatographic
retention time
3) Dielectric constant
4) Diffusion coefficient
5) Dissociation constant
6) Melting point
7) Reactivity
8) Solubility
9) Stability
10) Thermodynamic
properties
11) Viscosity
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5.  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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6.  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].
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7.  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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8.  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.
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9.  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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10.  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].
10Government College Of Pharmacy, Amravati.

11.  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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12.  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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13.  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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14.  [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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15.  [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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16. THANK YOU 16GovernmentCollege Of Pharmacy,Amravati.