Drug design
Drug design is an effort to develop a new drug by molecular modification of a lead compound with maximum effectiveness & greater level of activity.
Lead compound
Lead compound is a compound having particular biological activity obtained from natural or synthetic sources.
Example: Sulfanilamide was synthesized in 1908 but its antimicrobial activity for which sulfanilamide is a lead compound was discovered in 1932. Later numerous antibiotics have been developed from it.
Sulfanilamide …>…………….…>…sulfamethoxazole
[Lead compound] [Developed drug]
Nature gives us an idea of designing a new drug
Idea of designing new drugs can also be obtained from the nature. Various compound of varying therapeutic activity are produced by simple molecular modification in nature. For example a little molecular variation of the nature opium alkaloids shows the following variation of pharmacologic activity.
Morphine
• It is a potent analgesic.
• 10 times more potent then codeine.
Codeine
• Potent antitussive.
• Mild analgesic.
Thibaine
• CNS stimulant.
• Neither analgesic nor antitussive.
# Sex hormones contain cyalo-pintano-perhydro-phenanthene nucleus & a little variation may proceed to different drugs.
Testosterone
• Essential in spermatogenesis.
• Development in male sex organs & secondary sex characteristics.
• Increase libido.
Progesterone
• Helps to promote the development of a secretary endometrium that can accommodate implantation of a nearly forming embryo.
• Maintains endometrium in a favorite state of pregnancy.
Estrogen
• Development of secondary sexual characteristics of female.
• Reduces estroses.
Genesis of drugs
Drugs find their way into therapeutics mainly by one of the following routes:
1. Serendipity.
2. Random screening.
3. Extraction of active principle from natural sources.
4. Molecular modification of known drug.
5. Selection or synthesis of soft drugs.
6. Drug latentiation.
7. Rational design.
[1] Serendipity
Some drugs or novel uses of known drugs were discovered by accident in the laboratory or clinic by pharmacists, chemists, physicians and other investigators.
• The anti-inflammatory, analgesic, & anti-pyretic activities of phenylbutazone were discovered while it was being used solely as a solubilyzing agent for aminopyrine.
• The antibacterial action of penicillin was first noted by Fleming in 1929 in a culture of bacteria that was contaminated by fungus.
• The antidepressant properties of iproniazid were noted by fox in 1952 during its test as a tuberculostatic agent this discovery resulted in the development of MAO inhibitors.
[2] Random screening
In this approach to discover new drugs, all available chemical substances are submitted to a variety of biological test in the hope that some may show useful activity. This way of finding new drugs is not rewarding. It is estimated that for a new anticonvulsant to emerge through this process, it might be necessary to screen 500000 chemical compounds.
[3] Extraction from natural sources
For century’s humankind has used extracts from plant sources or animal organs for the treatment of various diseases. Owing to the good effects produced by these & similar remedies, folk medicine around the world has been extensively explored. Several drugs used today, especially antibiotics, vitamins & hormones resulted from purification of such extracts & isolation & identification of their active principles.
Our planet shelter approximately 600000 vegetable species [of which 250000-500000 are higher plant] but less then 10 % have been studied scientifically under the chemical & pharmacological aspects. It is hoped; therefore the therapeutic armamentarium will be gradually enriched with new drugs obtained from plants as a consequence of investigations in this field.
[4] Molecular modification
This method of obtaining new drugs also called molecular manipulation, method of variation, mechanistic method, selective process or approach, is the most used & as of the present, it is the most productive of new drugs.
Molecular modification is a natural development of organic chemistry. Basically, it consists of taking a well established chemical substance of known biological activity as a lead or prototype & then synthesizing & testing its structural congeners, homolog or analogs.
Advantages of molecular modification
1. Greater probability of congeners, homolog & analogs having pharmacological properties similar to those of the prototype then the compound selected or synthesized at random.
2. Possibility of obtaining pharmacologically superior products.
3. Likelihood of the production of the new drugs being more economical.
4. Synthesis similar to that of the prototype with saving of time & money.
5. Data gather may help to elucidate structure activity relationship.
Objectives of molecular modification
1. To discover the essential pharmacophoric moiety that is that feature of the molecule which imparts pharmacological action to the drug.
2. To obtain drugs having more desirable properties then the prototype in potency, toxicity, duration of action, ease of administration or handling, stability, cost of production.
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