PHARMACOGNOSY I LECTURES - PowerPoint Presentation

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PHARMACOGNOSY I LECTURES

L.A. DILBREEN BARZANJI

Pharmacognosy

Pharmacognosy

may be defined as a branch

of bioscience

which treats in details

medicinal

and related products of

crude matters

obtained from

plant

,

animal

and

mineral

origins.

In

shorts, it is an objective study of crude drugs from natural sources treated

scientifically

and it encompasses the knowledge of the

history

,

distribution

,

cultivation

,

collection

,

processing for market

and

preservation

, the study of

sensory

,

physical

,

chemical

, and

structural

characteristic and

the use of crude drugs.

Pharmacognosy

also includes study of other materials used in pharmacy such as

suspending

,

disintegrating

and

flavoring agent

,

filtering aids

, etc.

and

substances like

antibiotics

,

allergens

,

hallucinogenic

and

poisonous

plants,

immunizing agents

,

pesticides

, raw materials for the production of

oral

contraceptives

.

The

word ‘Pharmacognosy’ had its debut in the early 19

th

century to designate the discipline related to medicinal plants; it is derived from the Greek

pharmakon

,

’a

drug

’, and

gignosco

, ‘

to acquire knowledge of

’. The term ‘Pharmacognosy’ was first coined by

Johan Adam Schmidt

(1759-1809) in his hand-written manuscript

Lehrbuch

der

Materia

Medica

.

Pharmacognosy

is closely related to

botany

and

plant chemistry

and, indeed, both originated from the earlier scientific studies on medicinal plants.

The

term ‘

natural products

’ used commonly in Pharmacognosy field; it refers to products from various natural sources, plants, microbes and animals.

Natural

products can

be:

an entire organism

(e.g. a plant, an animal or a microorganism),

a

part of an organism

( e.g. leaves of a plant),

an

extract of organism or part of organism

,

pure

compound

(e.g. alkaloids, flavonoids,

lignans

, steroids, etc.) isolated from plants, animals or microorganism.

Over last century, a number of

top selling drugs

have been developed from natural products.

Anticancer

drug

vincristine

from

Vinca

rosea

,

narcotic

analgesic

morphine

from

Papaver

somniferum

,

antimalarial

drug

artemisinin

from

Artemisia

annua

,

anticancer

drug

Paclitaxil

(

Taxol

®) from

Taxus

brevifolia

and

antibiotic

penicillin

from

Penicillium

ssp.

A complete understanding of medicinal plants involves a number of disciplines including

commerce

,

botany

,

horticulture

,

chemistry

,

enzymology

,

genetics

,

quality control

pharmacology

.

Pharmacognosists

with a multidisciplinary background are able to make valuable contributions to these rapidly developing fields of study and

pharmacists in general need to have a

knowledge

of, and to

give professional advice on

,

the many herbal preparations available to public.

Drug discovery:

Although

drug discovery may be considered to be a recent concept that evolved from modern science during the 20

th

century, in reality the concept of drug discovery dates back many centuries, and has its origin in nature

.

In

modern drug discovery and development process, natural products play an important role at the early stage of ‘

lead

’ discovery, i.e.

discovery of the active natural molecule, which itself or its structural analogues can be an ideal drug candidate.

It is estimated that

61 %

of

877

small molecule new chemical entities introduced as drugs worldwide during 1981-2002 can be traced back to or developed from natural products.

These

include

:

natural

products 6%,

natural

product derivatives 27%,

synthetic

compounds with natural-product-derived

pharmacophores

5%,

synthetic

compounds designed on the basis of knowledge gained from a natural product 23%.

Natural product drug discovery: the traditional way

In the traditional, rather more academic, method of drug discovery from natural products, drug

ragets

are exposed to crude extracts, and in the case of a

hit, i.e. any evidence of activity

, the extract of is fractionated and the active compound is isolated and identified.

Every

step of fractionation and isolation is usually guided by bioassays, and the process is called

bioassay guided isolation

.

The

following scheme presents an overview of a bioassay-guided traditional natural product drug discovery process.

Source materials (e.g. plant) extract(s) active extract(s) Chromatographic fractionation Active fraction(s) chromatographic fractions Isolation and purification Isolated compounds active compound(s) Identification by spectroscopic techniques, e.g. UV , IR , MS ,NMR Identified compound(s) identified bioactive compound(s)

bioassay

bioassay

bioassay

bioassay

extraction

Sometimes

,

a straight forward natural product isolation route

, irrespective of bioactivity, is also applied, which results in the isolation of a number of natural compounds (small compound

library

) suitable for undergoing any bioactive screening

.

However, the process can be

slow

,

inefficient

and

labour

intensive

, and

it does not guarantee that a ‘lead’ from screening would be chemically workable or even patentable

.

Natural product drug discovery: the modern process

Modern

drug discovery approaches involves

HTS

(

high

throughput screening

), where, applying full automation and robotics, hundreds of molecules can be screened using several assays within a short time, and with very little amounts of compounds.

In

order to incorporate natural products in the modern HTS programmes, a

natural product library

(a collection

dereplecated

natural products) needs to be built.

Dereplectaion

is the process by which one can eliminate recurrence or re-isolation of same or similar compounds from various extracts.

A number of hyphenated techniques are used for

dereplication

, e.g.

LC-PDA

( liquid chromatography-photo-diode-array detector),

LC-MS

(liquid chromatography-mass detector) and

LC-NMR

(liquid chromatography-nuclear magnetic resonance spectroscopy).

While in the recent past it was extremely difficult, time consuming and

labour

intensive to build such a library from purified natural products, with the advent of newer and improved technologies related to separation, isolation and identification of natural products; the situation has improved remarkably.

Now

, it is possible to build a ‘

high quality

’ and ‘

chemically diverse

’ natural product library that can be suitable for any modern HTS programmes.

Natural

product libraries can also be of

crude extracts

,

chromatographic fractions

or

semi-purified compounds.

However

, the best result can be obtained from a fully identified pure natural product library as it provides scientists with the opportunities to handle the ‘

lead

’ rapidly for further developmental work, e.g. total or partial synthesis, dealing with formulation factors,

in vivo

assays and clinical trials.

Source materials (e.g. plant) extract(s) Chemical fingerprinting or dereplecation, e.g. use of LC-PDA, LC-MS, LC-NMR dereplicated extractsrapid isolation and purification e.g. HPLC Identification by spectroscopic techniques, e.g. UV , IR , MS ,NMR isolated compounds identified compounds (compound library) HTS Generation of ‘hit”

Large-scale production of selected ‘hit’ compounds

Entry to the further developmental stages e.g.

preformulation

, formulation, in vivo assays, clinical trials, etc.