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In Silico screening and optimization of new anti-

tb drug leads from alkaloids extracted from
Alstonia scholaris
 Contents
Introduction
Methodology
Experimental
Results and Discussion
References
Introduction
Alstonia scholaris Family: Apocynaceae

Common Names : Blackboard tree, Indian devil tree,

Milkwood pine, White cheesewood
Malayalam : Ezhilam pala, Yakshippala, Daivappala, Pala
Sanskrit : Saptaparna, Sapthachada, Visalatvak, Chatraparna,
Suktiparna Hindi : Chattiyan, Saitan ka jat
Alstonia scholaris is an evergreen tropical tree native to the
Indian subcontinent and Southeast Asia.In India the bark of
Alstonia scholaris is used solely for medicinal purposes, ranging
from Malaria and epilepsy to skin conditions and asthma. In
Ayurveda it is used as a bitter and as an astringent herb for
treating skin disorders, malarial fever, urticaria, chronic dysentery,
diarrhea, in snake bite and for upper purification process of
Panchakarma . The Milky juice of the tree is applied to ulcers.

Butanolic extracts of the bark of Alstonia scholaris (Malayalam

– Ezhilampaala) are recently found to be effective against drug
resistant Mycobacterium tuberculosis by in vitro bioassay. [1] The
alkaloids Nareline and Scholariscine are already isolated and
characterized from the plant.[2]Both these compounds are similar
to antibiotic Tigecycline (Tannimotto coefficients 0.551 and
0.621) having 30S ribosomal proteins as targets .[3]
 Methodology
1.Selection of Alkaloid- Scholariscine
2.Determination Similar drug from Drug Bang using
similarity Search
3.Identification target
4. Modelling of Target
5.Identification Of Binding site
6.Docking
7. Lipinsky Screening
Experimental
On analysing the result of similarity search, highest Tannimotto
coefficient of 0.62 was exhibited by the well known Drug Tigecycline.
Tigecycline, inhibits protein translation in bacteria by binding to the
30S ribosomal subunit.Using BLAST- Chain L, Crystal Structure Of
The Bacterial Ribosome From Escherichia Coli was sequentially
similar to 30S ribosomal subunit of Mycobacterium tuberculosis
 Using Uniprot FASTA sequence of 30S ribosomal of
Escherichia Coli.

3D structure of the target produced through SWISS

Modelling.
Binding site of the target identified by Pocket
finder.
Docking
Scholariscine and Modified Scholariscine were docked with
target by using Argus lab.

OH Scholarisci Modified Scholariscine

ne F
CH3
NH O NH

O
CH3
N N OH
H
OH CH3
 Scholariscine +
Target

Modified Scholariscine+ Target

Lipinsky Screening

Lipinski's Rule of Five

It is a rule of thumb to evaluate druglikeness or

determine if a chemical compound with a certain
pharmacological or biological activity has properties
that would make it a likely orally active drug in humans.
The rule was formulated by Christopher A. Lipinski in
1997
Scholarisci Modified
ne Scholariscine
Results and Discussion
Compound Binding Energy Molecular H-bond H-bond Log p Molar
Wt: donor Acceptor refractivity

Scholariscine -5.94973Kcal/mol 351 1 6 2.056 94.142

Modified -6.17832Kcal/mol 266 1 4 2.403 75.505

Scholariscine

Binding energy of Modified Scholariscine with Target is

less than Scholariscine.
Lipinsky screening shows that these two compounds are
pharmocologicaly active against Mycobacterium
tuberculosis
References
1. Molly Antony, Joel James, Chandra Shekhar Misra, Lipin Dev
Mundur Sagadevan, Arun Kumar Thaliyil Veettil2 & Thankamani
V., Anti Mycobacterial Activity Of The Plant Extracts Of Alstonia
Scholaris., International Journal of Current Pharmaceutical
Research

2. Abhijit Dey, Alstonia scholaris R.Br. (Apocynaceae):

Phytochemistry and pharmacology: A concise review., Journal of
Applied Pharmaceutical Science 01 (06); 2011: 51-57

3. Olson MW, Ruzin A, Feyfant E, Rush TS 3rd, O’Connell J,

Bradford PA: unctional, biophysical, and structural bases for
antibacterial activity of tigecycline. Antimicrob Agents Chemother.
2006 Jun;50(6):2156-66.
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