QUANTUM CHEMICAL, IN SILICO ADMET AND MOLECULAR DOCKING STUDIES ON MULTI TARGET NATURAL ANTIMYCOBACTRIAL AND ANTIVIRAL INHIBITORS FROM NATURAL LEADS

Supervised by:Dr. Sandeep PokhariyaAssistant professorChemistry section

Presented by:Tanushree Roll no.:15428BIF025Enrollment number : 33053

Introduction

TUBERCULOSIS: a mycobacterial disease• A pandemic disease caused by

Mycobacterium tuberculosis, an acid fast bacillus with unusual cell wall

• Responsible for pathogenicity, multiple drug resistance, cell permeability, immunoreactivity and inhibition of antigen responsiveness

• Also responsible for persistence and recrudescence

• Two strains identified : MDR & XDR• MDR: multiple drug resistance to

frontline antimicrobial drugs like rifampicin

• XDR: extensively drug resistant to second line antimicrobials

• Latent & active form of TB infection exists

AIDS: a viral disease• A widespread disease caused by HIV-1

& HIV-2 virus• Causes severe immunosuppression

through depletion of CD4+ cells• Its prolonged infection leads to

AIDS(Accquired immuno deficiency syndrome)

• May lead to health related problem such as pneumonia, thrush, fungal infection, TB, cancer, brain disease

• HIV-1: most commonly found worldwide

• HIV-2: found mainly in west Africa with some cases in India & Europe

Figure:1Mycobactrium figure

Figure : 2Region of Mycobacterium action on lungs

“◉ Figure: Life cycle of Mycobacterium

Figure 1:HIV virus structure

Figure 2:HIV virus life cycle

1

Figure: Life cycle of virus

“

Figure 1:Estimated absolute numbers of TB cases and deaths (in millions per year) 1990-2014

Figure 2:Male to female ratios of TB deaths among adults (aged ≥15 years), globally and by WHO region, 2014

Figure: TB treatment outcomes by HIV status, globally, 2013

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key concept using icons or illustrations

Figure:Percentage of TB patients with known HIV status by country, 2014

In 2014 ,6 million new cases reported of TB were reported, 80% belong to 22 countries

6 countries stand out largest – INDIA, INDONESIA, NIGERIA, PAKISTAN, PEOPLE’S REPUBLIC OF CHINA & SOUTH AFRICA

India with 23% , Indonesia and china with 10% each , out of total cases

A high rate of HIV co-infection ,especially in developing countries has infected the susceptibility of the population to Mycobacterium infection

In HIV patients population , TB treatment is complicated by undesirable drug-drug interaction that decrease the therapeutic concentration of anti retrovirals

Problem

Objective:QUANTUM CHEMICAL, IN SILICO ADMET AND MOLECULAR DOCKING STUDIES ON MULTI TARGET ANTIMYCOBACTRIAL AND ANTIVIRALINHIBITORS FROM NATURAL LEADS

Methadology: •Search of natural lead in citations

•Search of target molecule

•Quantum chemical calculation(Gaussian09W software package•Computer aided drug designing( in-Silico ADMET study)

•In Silico Molecular Docking (Autodock software

•Grid formation, •Running the docking algorithem and visualisation

Expected outcome

1. It will calculate electronic structure properties of antimycobacterial inhibitors

2. In Silico ADMET properties and molecular docking studies may provide

insight into the behaviour in terms of physio-chemical properties and interactions with residue at the active site of proteins

3. It may also provide a basis to corelate charge distribution with biological activity

4. Provides theoritical basis to design newer antimycobacterial and antiviral inhibitors

Significance◉ 1.provide a basis to corelate charge distribution in rection mechanism

◉ 2.to design newer antimycobacterial and antiviral inhibitors

◉ 3.May help to understand extent of interaction and other properties in one of the best interacting ligand protein instance

◉ 4.Help to deduce properties to be likliness of drug if better than the avilable drug in market

◉ 5.After passing all the steps it may enter into wet lab studies

◉ 6. Later it may enter into clinical trials

References• Mechanism of latency in Mycobacterium tuberculosis- NH Parrish, JD Dick, WR Bishai,

(1998)- Elsevier

• Tuberculosis and HIV co-infection: current state of knowledge and research priorities- sponsored by National Institute of Health Division of AIDS control-by G. Friedland(2007)

• Tuberculosis and HIV co-infection by Andrzej Pawlowski, Marine Jansson, Markus Skold, Martin E.Rottenberg , Gunilla Kallenius , febuary 12 2012

• WHO report 2006 report Geneva

• TB:IV – collaborative TB/HIV activities 2014 Tables, Graphs, Maps , Source: Global Tuberculosis Report 2015

Any questions ?

Thanks!