CHEARS

PART-1 : DRUG DISCOVERY

DRUG

A drug is a chemical compound which is in raw form and is used for the purpose of diagnosis, prevention, relief or cure of a disease in humans and animals.

MAIN STAGES OF DRUG DEVELOPMENT PROCESS

1.Drug discovery

2.Preclinical Trials

3.Clinical Trials

DRUG DISCOVERY:

o Drug discovery is the process by which drugs are discovered and designed.

o Identifying a compound therapeutically useful in curing and treating the disease.

AIM:

§ To develop effective and more safer drugs

§ To develop economical drugs

§ To discover new uses of already established the drugs.

§ To determine the mechanism of drug action

PROCESS OF DRUG DICOVERY:

§ HTS- High throughput screening -Screening more than 50,000 compounds in a day.

§ CADD –Computer Aided Drug Design-Identify lead compound

§ Time consuming- (10-12 years)

§ More expensive to identify one drug may be it costs around 800 million

STAGES OF DRUG DISCOVERY:

How the drugs are to be identified?

1.TARGET IDENTIFICATION:

First of all select the disease and find out the causes of disease,it may be a genetic disease or environmental disease or infectious disease.

For example: Disease :Tuberculosis

Causes: Mycobacterium tuberculosis.It is a bacterial infection.It caused by smoking and undernutrition. TB is spreads from one person to other through air.

2.TARGET VALIDATION:

Now,validate the found target it may be gene or protein.Then select the protein to bind the particular randomly selected compounds. Then,validate which protein or gene shows Drug ability.It validate to test more than 50,000 of compounds in a day,it is called High throughput screening.

For example:

Targeted infection: Mycobacterium tuberculosis. Now,validate more than 1000 of compounds to screen the infection,which compound is binding the particular gene and gives drug affinity.

Drugs or chemical compounds work by binding to specific receptors and activating them is called drug affinity.

3.LEAD IDENTIFICATION:

The chemical compound potential to bind to the identify the target successfully.

Methods of Lead Identification.

A) FROM NATURAL SOURCES:

§ Plants are considered as the primary and the oldest source of drugs.

§ Example:

§ ASPIRIN- salix found in willow bark.Aspirin is used for pain relief and antiplatelet drug.

§ COCAINE-It is derived from the coca plant.It is used for anaesthesia and recreational drug.

§ Digitalis-It is derived from Foxglove (Digitalis Purpurea).Digitalis is used to treat arrhythmia.

§ Morphine-It is derived from the Opium poppy(Papaver somniferum)

§ Caffeine-Found in coffee beans,tea leaves,cacao pods,kola nuts and garana.It is used to treat fatigue and migraines.

B) RANDOM SCREENING/NON-TARGETTED SCREENING:

All compounds including synthetic chemicals, natural products of plants marine and microbial origin from a given series are tested.Inspite of budgetary and manpower overuse,this method may be used to discover drugs or leads that have unexpected activities.

Example:

§ CYCLOSPORIN was discovered during the screening of fungal products.It is an immunosuppressant drug.

§ The drug obtained from the marine organisms which are being conventionally used like shark and cod liver oils,sodium alginate,agar-agar,chitin etc.

§ SIMULARIN-source-soft coral sinularia fleibilis.It is used for Anticancer drug.

§ ASPERDIOL-source-found in gorgonian coral Eunicea Knighti.It is used for Leukemia.

§ VARIABILIN: Source-sponge,Ircinia oros.It is used as an Antibiotic.

C) SERENDIPITY:

Serendipity is when someone accidently finds something good.Is an unplanned fortunate discovery.Serendipity is also called Happy accident.

For Example:

§ METHOTREXATE (Anticancer drug) –was discovered while studying leukemia and it is being used to treat Psoriasis.

§ VINBLASTINE- was first discovered while studying a plant’s antidiabetic effect.

§ MUSTIN-discovered in 1940,was used on enemy in wars which is used as an anticancer therapy.

§ CISPLATIN-used as a Chemotherapy for Bladder cancer,discovered while studying E.coli bacteria

§ INSULIN- was discovered while studying the structure of the pancreas.

D)MOLECULAR MODIFICATION:

Molecular modification is chemical alteration of a known and previously characterized lead compound for the purpose of enhancing its usefulness as a drug.

Chemical analogues are prepared from already existing drugs by a technique called molecular modification.

§ For example:

§ Hydrogenated compound of chlorthiazide exhibits increased potency and less side effects than chlorthiazide.

§ ATROPINE ,Changing the slight variation in chemical structure the drug Cocaine discovered.

§ Morphine is used as an important agent for the relief of pain.Adding the methane compound and removing hydroxyl compound the drug Codeine was found. Codeine is used for relief mild pain and as an antitussive agent.

4.LEAD OPTIMIZATION:

The new chemical entities discovered by the methods described above are selected and compared with one another and the compound exhibiting greater potency than the existing drugs and which can we developed in to a safe and effective medicine is selected.

§ In a simple way the compound was shortlisted the structure and optimized.

§ Various in vivo and in vitro test are performed for comparing the leads to determine their metabolic stability and their effects on the body.

§ The selected chemical compounds tested in Laboratory methods.

§ Blood and urine samples are analyzed and finally the compound which is therapeutically useful .

§ Which compound given the therapeutic effect of the particular disease,that chemical compound selected as a medicine.

To be continued....