Acridones the Fore Vision

8/8/2019 Acridones the Fore Vision

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Phyto Medicines-The Fore Vision

Special Lecture on Acridones

Dr.K.Balasubramanian

Visiting Professor,

CBT,Anna University,Chennai-600025.

[email protected]


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Acridones the Fore Vision

Modern biomedicinal research with acridones

began with plant secondary metabolites but

the successful development of these alkaloids

into drugs has yet to be realized. However,

there are synthetic acridones unrelated to the

natural products now emerging as promising

bioactive compounds.


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Fore Vision

The purpose of this lecture is to

highlight the renewed interest in

acridones for multi targeted drug

research, with the emphasis

placed on several derivatives inearly stage development .


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Anti-Herpes Acridones

Novel anti-herpes acridones

developed using a ligand-based

approach have much simpler

structure and generally have

higher selectivity than thecorresponding alkaloids.


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Natural Acridones

Three sub-types are currently classified on thebasis of activity against Herpes Simplex Virus(HSV) and, or Human Cytomegalovirus

(HCMV) and all of them inhibit viral replicationpost-adsorption. In terms ofmode/mechanism of action, this "secondwave" of early generation lead molecules

appears unique in comparison to the naturalproducts and to drugs derived from moretraditional templates.


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Plant based Acridones


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Acridones the Fore Vision


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Pharmacological Activity

Acridones have unique molecular structure.

They are bioisostre of Xanthones.

Activity is based on 9th and 10th position. The activities they possess include Anti-Cancer

Anti-Viral ,Anti-Herpes ,Anti-malarial ,

Anti-neoplastic besides their basic Anti-bacterial and Anti-fungal properties.


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Natural sources


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Natural Acridones


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Natural Acridones


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Journey of Acridones


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Inhibition of HSV replication by these agents is

best understood and it occurs after viral DNA

synthesis. The mechanism for one prototype

inhibitor (5-chloro-1,3-dihydroxy acridone),

involves a blockade of viral DNA maturation

(cleavage/packaging) and viral capsids

accumulate abnormally. Interestingly, the 7-Chloro regioisomer blocks a later stage of viral

assembly.


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SAR towards Fore Vision


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SAR the fore vision


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Activity oriented Acridones


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Herpes Simplex Virus (HSV) infections are

among the most common human diseases.

We assess the structural features and

electronic properties of a series of ten 1-

hydroxyacridone derivatives (1aj) recently

described as a new class of non-nucleoside

inhibitors of Herpes Simplex Virus-1 (HSV-1).


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Based on these molecules, we applied rigid

analogue and isosteric replacement

approaches to design and synthesize nine new

3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine

derivatives (2ai). The biological and

computational results of these new molecules

were compared with 1-hydroxyacridones.


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we applied rigid analogue and isostericreplacement approaches to design andsynthesize nine new 3H-

benzo[b]pyrazolo[3,4-h]-1,6-naphthyridinederivatives (2ai). The biological andcomputational results of these newmolecules were compared with 1-

hydroxyacridones and confirmed theirpotential antiviral profile.


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An inhibitory profile was observed in 10-Clsubstituted 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine derivative (2f), which presentsthe same substituent at the analogous positionof1-hydroxyacridone derivative (1b). Thestructureactivity relationship (SAR) studiespointed out the 10-position next to nitrogenatom as important for the anti-HSV-1 profile in

the pyrazolo-naphthyridine derivatives tested,which reinforced the promising profile forfurther experimental investigation.


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The most potent acridone and pyrazolo-

naphthridine derivatives were also submitted

to an in silico ADMET screening in order to

determine their overall drug-score, which

confirmed their potential antiviral profile.


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ACRIDO AZETIDIN-2-ONES - A

NOVEL APPROACH FOR NEW

ANTI DIABETIC AGENT


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Docking with Dopamine receptor-9.60746 Kcal/mol (dopamine receptor)

-8.96353 Kcal/mol (Heat Shock Protein

90)

-10.0094 Kcal /mol

-10.391 Kcal/mol

4

3 2

N1

O2 6

S1 9

20

2 1 22

2 3

242 5

5

1 2

7

13

6

1 41 0

9

1 1

N8

17

16

18

15

C H 327

O28

N

O

S

N

CH3

OCH3

N

O

S

O


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BISPHOSPHOACRIDONE (BA)

Bisphosphoacridone : A prospective approach

as a novel antineoplastic agent.


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DOCKING IMAGEFarnesyl pyrophosphate (FPP) synthase


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HSP90


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HSP 90

-12.6325 Kcal/mol

High binding energy

IUPAC Name : 10[2-oxo-4-

(phenylsulfanyl)cyclobutyl]acridin9(OH)-one

N

O

S

O

H

MILECULAR DOCKING:

To find the affinity of ligand towards receptor.

RECEPTOR : HEAT SHOCK PROTEINS (HSP 90)


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Docking details in HSP90

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Acridones the Fore Vision