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Medicinal Chemistry
Medicinal Chemistry
MEDICINAL PLANTS
HISTROY
In the early years, there is little written evidence of the use of herbs in medicine as it
was usual to pass on knowledge verbally; as knowledge grew written records began to
emerge. Herbs were of significant importance as they were used not only for medicine
but also in magic and ceremonies. As far back as 3000 B.C., medical treatments are
shown on Babylonian clay tablets, prior to the importation of herbs.
One of the most famous written records of the Chinese use of herbs is the
Canon of Herbs, the result of the knowledge of the emperor Shen Nung who died in
2698 B.C. It is compiled of 252 plant descriptions, including medicinal effects,
growing locations, use and preservation, in fact a blueprint for future pharmacopoeias.
Ayurvedic medicine was practiced in India as far back as 5000 years ago and
one of the oldest known Indian books on plants, Vedas, records the medicinal and
religious use of herbs and plants. The most famous of the ancient Romans writings on
the medicinal use of herbs is recorded by Dioscorides in De Materia Medica,a book
filled with descriptions of hundreds of healing plants. This book was widely
referenced until the seventeenth century.
John Gerard (1545- 1612) was a highly respected English herbalist of the 16th
century; in 1596, he was first credited with publishing records of the plant species
found in his garden, at Holburn, but it is for his later publication in 1597, the Herball,
for which he is most remembered.
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Definition of a Herb
Today, the term 'herb' is more commonly used to describe 'any seed-bearing plant
which does not have a woody stem and dies down to the ground after flowering' or
'any plant with leaves, seeds or flowers used for flavoring, food, medicine or perfume'.
ATROPINE
Medicinal value
RAUWOLFIA SERPENTINA
Alkaloid Reserpine.
Medicinal value
Antihypertension.
CINCHONA TREE
Alkaloid Cinchonine
3
Medicinal value
Treatment of Malaria.
Medicinal value
Medicinal value
Medicinal value
Anti-hypertensive
Anti-hepatotoxic- Act against liver damage
4
Medicinal value
Medicinal value
Antidiabetic
Treatment of Hodgkin’s disease (Lymphoma-type of cancer originates
from WBC).
Treatment of Leukemia ( cancer)
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ANTIBIOTICS
In common usage, an antibiotic (from the Ancien Greek: ἀντί – anti, "against", and
βίος – bios, "life") is a substance or compound that kills, or inhibits the growth of,
bacteria. Antibiotics belong to the broader group of antimicrobial compounds, used to
treat infections caused by microorganisms, including fungi and protozoa.
to antibiotics by the Kirby-Bauer disk diffusion method. Antibiotics diffuse out from
antibiotic-containing disks and inhibit growth of S. aureus resulting in a zone of
inhibition
CLASSIFICATION OF ANTIBIOTICS
Natural - Bacitracin
Semisynthetic – Benzyl penicillin
Synthetic – Chloramphenicol.
Antibiotics may be divided into two broad groups according to their effect on
microorganisms:
Dr. Ehrlich noted that certain dyes would bind to and color human, animal or
bacterial cells, while others did not. He then extended the idea that it might be
possible to make certain dyes or chemicals that would act as a magic bullet or
selective drug that would bind to and kill bacteria while not harming the human host.
After much experimentation, screening hundreds of dyes against various
organisms, he discovered a medicinally useful drug, the man-made antibiotic,
Salvarsan. However, the adverse side-effect profile of salvarsan, coupled with the
later discovery of the antibiotic penicillin, superseded its use as an antibiotic.
Arsphenamine was marketed under the trade name Salvarsan in 1910. It was
also called 606, because it was the 606th compound synthesized for testing. Salvarsan
was the first organic anti-syphillitic, and a great improvement over the inorganic
mercury compounds that had been used previously. A more soluble (but slightly
less effective) arsenical compound, Neosalvarsan, (neoarsphenamine), became
available in 1912.
PENICILLIN
PENICILLINE
In the basic skeleton it contains a five membered thiazolidine ring and a four
membered beta-lactam ring.
CH2
Eg: If R = , the drug is benzyl penicillin.
If R =
HO CH
If R=
CH
PENICILLIN
Natural penicillin are said to be acid and base unstable. Instability in acid media
logically terminates its oral administration due to the highly acidiC pH of the gastric
juice in stomach.
Penicillin under acidic pH condition is converted to penillic acid which has no drug
activity. Similarly under basic condition it is converted to penicilloic acid which
again does not have any drug activity.
Beta- Lactamase enzyme cleaves the beta-lactam ring and thereby making the
drug inactive.
MEDICAL APPLICATION
MASS PRODUCTION
The narrow range of treatable diseases or spectrum of activity of the penicillins, along
with the poor activity of the orally active phenoxymethylpenicillin, led to the search
for derivatives of penicillin that could treat a wider range of infections. The isolation
of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic
penicillins, with various improvements over benzylpenicillin (bioavailability,
spectrum, stability, tolerance).
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The first major development was ampicillin, which offered a broader spectrum
of activity than either of the original penicillins. Further development yielded beta-
lactamase-resistant penicillins including flucloxacillin, dicloxacillin and
meticillin.
MECHANISM OF ACTION
Gram-positive bacteria are called protoplasts when they lose their cell wall.
Gram-negative bacteria do not lose their cell wall completely and are called
spheroplasts after treatment with penicillin.
ADVERSE EFFECTS
Common adverse drug reactions (≥1% of patients) associated with use of the
penicillins include diarrhea, hypersensitivity, nause, rash, neurotoxicity. Infrequent
adverse effects (0.1–1% of patients) include fever, vomiting, dermatitis, seizures
ANTIBIOTIC MISUSE
The first rule of antibiotics is try not to use them, and the second rule is try not to
use too many of them.
STREPTOMYCIN
MECHANISM OF ACTION
TREATMENT OF DISEASES
CHLORAMPHENICOL
HISTORY
ADVERSE EFFECTS
The most serious adverse effect associated with chloramphenicol treatment is bone
marrow toxicity, which may occur in two distinct forms: bone marrow suppression,
which is a direct toxic effect of the drug and is usually reversible, and anemia, which
is (rare, unpredictable, and unrelated to dose) and generally fatal.
SPECTRUM OF ACTIVITY
MECHANISM OF ACTION
THERAPEUTIC USES
The original indication of chloramphenicol was in the treatment of typhoid, but the
now almost universal presence of multi-drug resistant Salmonella typhi.
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TETRACYCLINES
HISTORY
MECHANISM OF ACTION
ADMINISTRATION
ANTIVIRAL AGENTS
Virus
COMPOSITION
Viruses do not possess cell wall. Viruses consist of either DNA or RNA
enclosed in a shell of protein known as CAPSID. The capsid is composed of
several sub-units known as capsomeres that decide the shape of the capsid.
Though often spherical, capsid may possess different shapes. In certain cases,
capsid may be surrounded by an outer protein of lipoprotein envelope. This
encircling membrane may be called as envelope.
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VIRAL DISEASES
CLASSIFICATION OF VIRUSES
Various antiviral agents are found to possess very narrow spectrum of activity. The
development of antiviral agents having selective toxicity to viral cell leaving host cells
unaffected still remains a dream.
N
HN
H2N N
N
CH2OCH2CH2OH
MODE OF ACTION
ACYCLOVIR
ACYCLOVIR TRIPHOSPHATE
The affinity of viral thymidine kinase enzymes for acyclovir is 200 times greater than
that of Mammalian enzymes.
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VIRAL REPLICATION
MEDICAL APPLICATION
ANTIPYRETIC ANALGESICS
Antipyretic analgesics are also known as febrifuges. They are defined as drugs
that lower the temperature of the body in PYREXIA (situations when body
temperature has been raised above normal).
They exert their action on the heat regulating centre in the hypothalamus.
CLASSIFICATION
Cohn and Hepp first identified the powerful antipyretic activities in both
aniline and acetanilide. The ortho, meta and para amino phenols are reported to be
relatively less toxic than aniline. The para- isomer is found to be the least toxic.
Eg.,
Paracetamol
HO NHCOCH3
Salicin was the first compound belonging to this category that exhibited
medical value. It was used as a substitute for quinine as a febrifuge. Acetyl salicylic
acid of aspirin was first synthesized by Gerhardt in 1852. The name aspirin originated
form the old name of salicylic or spiric acid, obtained from spirea plants.
Eg.,
Aspirin
COOH
OCOCH3
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3. Quinoline derivatives:
The historical importance and utility of quinine was known in the medical
practice for a long time as a potent antipyretic in addition to its remarkable effect
against the malarial fever. Two quinoline derivatives first synthesized though
possessed significant antipyretic action, yet could not gain importance as drug because
of their high toxic effects on the red blood corpuscles and damaging after-effect on
kidneys. Eg., Thalline.
One of the first and foremost synthetic organic compounds which were
successfully used as drugs was found to be a heterocylce.
Eg.,
Phenylbutazone
N
O
N
H3CH2CH2CH2C O
5. N-Arylanthranilic acids:
NH
H3C CH3
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It is analgesic drug usually used for the treatment of mild pain and pain due to
dental extractions.
MODE OF ACTION
NARCOTIC ANALGESICS
(Opiate analgesics)
The opium class of narcotic drugs are considered not only as the most potent
and clinically useful agents causing depression of central nervous system, but also as
very stong analgesics. Morphine and morphine like drugs are referred to as opiods or
opiates. They are also known as narcotic analgesics (narcotic derived from the Greek
word ‘narcotuc’ meaning drowsiness).
Morphine and morphine like drugs may not alter the sensation of pain but they
modify the emotional reaction to pain. The pain may be present but may not be felt as
painful.
Morphine
Codeine
The seriousness and enormous after effects of steroid therapy necessitated the
development of non-steroidal anti-inflammatory drugs.
Eg.,
Ibuprofen:
It is an anti-inflammatory drug that possesses anti-pyretic and analgesic
actions. It is used for the treatment of rheumatoid arthritis and osteoarthritis.
Diclofenac Sodium:
It has analgesic, antipyretic and anti-inflammatory actions. It is mostly
employed in the treatment of rheumatoid arthritis and other rheumatic disorders.
ANTIHISTAMINES
CLASSIFICATION
GENERAL ANAESTHETICS
CLASSIFICATION:
1. Inhalation anaesthetics
2. Intravenous anaesthetics
3. Basal anaesthetics.
1. INHALATION ANAESTHETICS
Inhalation anaesthetics could be either volatile liquids or gases and they are
administered through inhalation process. Eg:
a) Ether:
CH3CH2OCH2CH3
It still continues to be employed as an anaesthetic for producing insensitivity to pain
in surgical trauma.
b) Nitrous oxide:
N2 O
It is the weakest but the safest inhalation general anaesthetic. It is usually
administered in conjunction with other potent inhalation anaesthetics such as
halothane. Some patients often get an attack of hysteria and for this reason it is
invariably termed as laughing gas. In is an inhalation anaesthesia of choice in dental
surgery.
2. INTRAVENOUS ANAESTHETICS
Ketamine hydrochloride
It is rapid acting general anaesthetic drug which cause anaesthesia
accompanied by deep analgesia. It is an intravenous anaesthetic of choice for surgical
operations of short duration.
3. BASAL ANAESTHETICS
Basal anaesthetics are agents which induce a state of unconsciousness but the
depth of unconsciouness is not enough for surgical procedures. They are often used to
induce basal anaesthesia before the administration of inhalation anaesthetics. They are
often administered through rectum.
Fenatyl Citrate
It is employed basically as an analgesic for the control of pain associated with
all kinds of surgery. It may be used along with all drugs commonly employed for
general anaesthesia.
LOCAL ANAESTHETICS
Local anaesthetics are used to abolish the sensation of pain in a restricted area
of the body and for minor surgical operations when loss of consciousness is not
desirable. The area is determined by the site and the technique of administration.
Usually smaller diameter nerve fibres are more susceptible to the action of local
anaesthetics than the larger diameter ones.
CLASSIFICATION
2. Infilteration Anaesthesia
The drug is injected subcutaneously to paralyze the sensory nerve endings
around the area to be rendered insensitive. Eg., for tooth extraction.
4. Spinal Anaesthesia
The drug is injected into the cerebral spinal fluid to paralyse the roots fo the
spinal nerves. Eg., Induce anaesthesia for abdominal and pelvic surgical operations.
5. Epidural Anaesthesia
This is special type of nerve block anaesthesia in which the drug injected into
the epidural space. Eg., the roots of spinal nerves are anaesthetized.
PROCAINE HYDROCHLORIDE
It is one of the least toxic and most commonly used local anaesthetics. The
salient features for its wide popularity is attributed to its lack of local irritation,
minimal systemic toxicity, longer duration of action and low cost. It is effectively
used for causing anaesthesia by infilteration, nerve block or spinal anaesthesia.