Antibiotics: a substance produced by one microorganism that

selectively kills or inhibits the growth of another.

Classification
Penicillin – widely used to treat a variety of infections, including skin
infections, chest infections and urinary tract infections.
Aminoglycosides – tend to only be used to treat very serious illnesses such as
septicaemia, as they can cause serious side effects, including hearing loss and
kidney damage; they break down quickly inside the digestive system, so they
have to be given by injection, but are also used as drops for some ear or eye
infections.
Tetracyclines – can be used to treat a wide range of infections; commonly
used to treat moderate to severe acne and rosacea, which causes flushing of
the skin and spots.
Macrolides – can be particularly useful for treating lung and chest infections; can also be a
useful alternative for people with a penicillin allergy or to treat penicillin-resistant strains of
bacteria.
Fluoroquinolones – broad-spectrum antibiotics that can be used to treat a wide range of
infections.
Cephalosporins – can be used to treat a wide range of infections, but are also effective for
treating more serious infections, such as septicaemia and meningitis.
 Penicillins
• The penicillins are the oldest class of antibiotics.
Penicillins are bicyclic penam compounds and
share their chemical structure with the
cephalosporins.
• Penicillins are generally bactericidal, inhibiting
the formation of the bacterial cell wall. Penicillins
are used to treat skin infections, dental infections,
ear infections, respiratory tract infections, urinary
tract infections, and gonorrhea.

Penam = compound comprising a beta-lactam ring fused to a saturated 5-membered ring

containing one sulfur atom.
Penicillin is also known by the name of Penicillin V or
phenoxymethylpenicillin. It is used to treat infections caused by different
bacteria. Penicillin is also the name of the class of antibiotics that have
core-structures known as beta-lactams. The penicillin is excreted by
some fungi of the genus Penicillium.

Formula and structure: Penicillin chemical formula is

C16H18N2O5S and it molar mass is 350.389 g mol-1.
The molecule is formed by three carboxylic group,
one of them corresponding to the carboxylic acid
moiety. The molecule is mostly planar: in one
extreme there is an aromatic ring and in the other
part there are two hetero rings fused to form a β-
lactam group (in red color). Its chemical structure can
be written as below, in the common representations
used for organic molecules.
Penicillin V is used in the treatment of some infections, particularly skin, throat
and ears infections. The penicillin V is only ingested by mouth, while other
penicillins are injected on patients. The antibiotic works against infections caused
by Streptococcus pyogenes and tonsillitis
Tetracyclines
• Tetracyclines are an old class of antibiotics. They got
their name for their chemical structure which
contains four hexagonal rings. Tetracyclines are
derived from a species of Streptomyces bacteria.
• Tetracycline antibiotics are bacteriostatic agents and
work by inhibiting the bacterial protein synthesis via
interaction with bacterial ribosome. Tetracyclines are
effective against a wide variety of microorganisms,
including spirochetes, atypical bacteria, rickettsia, and
amebic parasites.
• Current applications of tetracyclines include
treatment of peptic ulcer disease as part of a multi-
drug regimen, infections of the respiratory tract,
cholera, traveler’s diarrhea, malaria prophylaxis. Their
most common current use is in the treatment
of acne and rosacea.
Aminoglycosides
• Aminoglycosides are derived from various species
of Streptomyces.
• In 1943, Selman Waksman, together with his co-workers,
discovered that a bacterium Streptomyces griseus produced an
antibiotic substance which they named "streptomycin." Selman
Waksman was awarded the Nobel Prize in Physiology or
Medicine in 1952 for his discovery of streptomycin.
• The aminoglycosides are bactericidal and work by binding to the
bacterial ribosome, thus stopping bacteria from making
proteins.
• Aminoglycoside antibiotics are used to treat infections caused
by gram-negative bacteria. Aminoglycosides may be used in
combination with penicillins or cephalosporins to ensure better
antimicrobial coverage. Aminoglycosides work quite well, but
bacteria can become resistant to them. Since aminoglycosides
are broken down easily in the stomach, they can't be given by
mouth and must be injected. Generally, aminoglycosides are
given for short time periods.
The term aminoglycoside is derived from the chemical structure of
these compounds, which are made up of amino groups (―NH2)
attached to glycosides. The first aminoglycoside, the streptomycin,
was discovered in 1943 by American biochemists Selman
Waksman, Albert Schatz, and Elizabeth Bugie, who isolated
the compound from Streptomyces griseus, a strain of soil bacteria.
Streptomycin was found to inhibit the growth of a variety of
bacterial organisms, including the organism that causes tuberculosis

Streptomycin
Or
 Prodrugs
• A prodrug is a medication or compound that,
after administration, is metabolized (i.e., converted within
the body) into a pharmacologically active drug.

Barrier

Barrier … Physicochemical, Biopharmaceutical, or pharmacokinetic obstacle

Aspirin is a prodrug, which is transformed into salicylate in the
stomach, in the intestinal mucosa, in the blood and mainly in the
liver. Salicylate is the active metabolite responsible for most anti-
inflammatory and analgesic effects.
GI…. Gastrointestinal
Drug Design or Rational Drug Design
Rational drug design refers to the development of medications based
on the study of the structures and functions of target molecules. That
is to say, the role of rational drug design is to use a methodological
approach to coming up with a new drug, as opposed to blindly hoping
some stroke of luck helps design a new drug, or instead of randomly
testing hundreds of drug molecules in hopes that one of them binds
to a receptor and exerts a therapeutic effect.
During rational drug design, researchers take three general steps to
create a new drug:
Step 1. Identify a receptor or enzyme that is relevant to a disease they
are going to design a drug for.
Step 2. Elucidate the structure and function of this receptor or
enzyme.
Step 3. Use the information from step two in order to design a drug
molecule that interacts with the receptor or enzyme in a
therapeutically beneficial way.
This seems easy, but it does have to take a lot of important factors into
account. For example, researchers must account for whether or not the
drug will bind to a specific molecule or more than one. Binding to other
molecules might bring about more adverse effects. How well the drug
will bind to the target molecule needs to be clarified. If it can't bind to
the target well, it might be useless.
The shape and charge of the molecule must be examined in order to
determine how this might affect the way it not only binds to the target,
but is absorbed, distributed, metabolized, and excreted by the body.

A pharmacophore is an abstract description of molecular features

that are necessary for molecular recognition of a ligand by a
biological macromolecule
 Two major types of drug design

1. Ligand-based
Ligand-based drug design (or indirect drug design) relies on
knowledge of other molecules that bind to the biological target of
interest. These other molecules may be used to derive
a pharmacophore model that defines the minimum necessary
structural characteristics a molecule must possess in order to bind
to the target. In other words, a model of the biological target may
be built based on the knowledge of what binds to it, and this model
in turn may be used to design new molecular entities that interact
with the target. Alternatively, a quantitative structure-activity
relationship (QSAR), in which a correlation between calculated
properties of molecules and their experimentally
determined biological activity, may be derived. These QSAR
relationships in turn may be used to predict the activity of new
analogs.
2. Structure-based
Structure-based drug design (or direct drug design) relies on
knowledge of the three dimensional structure of the biological
target obtained through methods such as X-ray
crystallography or NMR spectroscopy. If an experimental structure
of a target is not available, it may be possible to create a model of
the target based on the experimental structure of a related protein.
Using the structure of the biological target, candidate drugs that are
predicted to bind with high affinity and selectivity to the target may
be designed using interactive graphics and the intuition of
a medicinal chemist. Alternatively various automated computational
procedures may be used to suggest new drug candidates.
Current methods for structure-based drug design can be divided
roughly into three main categories. The first method is
identification of new ligands for a given receptor by searching
large databases of 3D structures of small molecules to find those
fitting the binding pocket of the receptor using fast
approximate docking programs. This method is known as virtual
screening. A second category is de novo design of new ligands. In
this method, ligand molecules are built up within the constraints
of the binding pocket by assembling small pieces in a stepwise
manner. These pieces can be either individual atoms or molecular
fragments. The key advantage of such a method is that novel
structures, not contained in any database, can be suggested. A
third method is the optimization of known ligands by evaluating
proposed analogs within the binding cavity.
 https://www.slideshare.net/rahulbs89/drug-design-and-discovery

https://www.slideshare.net/ZainabSaif/drug-designing-70306013

https://www.slideshare.net/bharathpharmacist/drug-design-43813649

https://en.wikipedia.org/wiki/Drug_design

Telomeres, repetitive (TTAGGG) DNA–protein complexes at the ends of

chromosomes, are crucial for the survival of cancer cells. They are
maintained by an enzyme called telomerase in the vast majority of tumors.

For example, the immortalisation of cancer cells could be attacked via the
targeting of telomerase, as it is both specific to cancerous cells and necessary
for their survival [15]; molecular alterations that deregulate growth can be
corrected, as with Imatinib’s targeting of the BCR-ABL protein in chronic
myelogenous leukaemia; or the tumour’s blood supply can be cut off by
preventing angiogenesis, as done by the drug Bevacizumab’s inhibition of
vascular endothelial growth factor A
 How exactly is a drug developed?

Step 1: Drug discovery and target validation

The first step in the drug development process involves discovery work. This is
where drug development companies choose a molecule, such as a gene or
protein, to target with a drug. This is also where the drug developer will
confirm that the molecule is indeed involved with the disease in question.
After testing multiple drug molecules, the drug development company will
choose those that have promise. Keep in mind it's not uncommon for drug
developers to have more than a handful of promising lead compounds at this
stage.
Step 2: Preclinical testing
This step is divided into two subcomponents: in vitro and in vivo testing. In
vitro testing examines the drug molecules' interactions in test tubes and within
the lab setting. In vivo testing involves testing the drug molecules on animal
models and in other living cell cultures. Although efficacy is beginning to be
established here, safety is paramount as the FDA will not let preclinical studies
move into human trials without extensive data on safety. This is the stage
where researchers will whittle thousands of drug molecule candidates down to
between one and five.
Step 3: Investigational New Drug application filing
The third step involves submitting an Investigational New Drug application to
the FDA prior to beginning human clinical trials. This is the point where the
FDA will scrutinize the results from the preclinical testing, look at side effects
and other safety features of an experimental drug, examine the drugs'
chemical structure and how it's believed to work, and take its first look at the
manufacturing process of the drug. If the FDA approves a drug developers' IND
then it can move onto human trials. An IND approval is also the point at which
a patented drugs' 20-year exclusivity period begins.
Step 4: Phase 1 clinical studies
The first phase of human clinical testing involves a relatively small group of
healthy people, usually a dozen to a few dozen, and it'll focus entirely on
safety. This stage of study involves looking at how a drug is absorbed and
eliminated from the body, as well as what side effects it may cause and
whether or not it's producing the desired effect. Phase 1 clinical studies are
also where maximum tolerated doses are established. It really is all about
safety, although it's not uncommon for drug developers to tout early signs of
efficacy in phase 1. If everything looks promising the study moves to phase 2,
or midstage trials.
Step 5: Phase 2 clinical studies
The two big changes between early stage and mid-stage trials are that the
patient pool widens from a few dozen to perhaps 100 or more patients, and
the patients being treated are no longer healthy volunteers but people being
afflicted by the disease in question. Safety remains a big focus of phase 2
studies, with short-term side effects being closely monitored, although an
increasing emphasis will begin to be placed on whether or not a drug is
working as expected and if it's improving the condition or not. Phase 2 studies
also establish which dose (if multiple doses were tested, as is often the case)
performed most optimally. If the experimental drug continues to look
promising it'll move onto late-stage studies.
Step 6: Phase 3 clinical studies
Safety and efficacy are monitored. Phase 3 studies are designed by drug
developers but approved by the FDA with guidelines for a clearly defined
primary endpoint to determine the success or failure of a tested drug. Phase 3
trials involve even more patients, perhaps a few hundred to maybe thousands,
and they are by far the longest and costliest of all components of the drug
development process. This is also the stage where drug developers will begin
to think about how they're going to ramp up production if the phase 3 results
are promising.
Step 7: New Drug Application filing
The seventh step in the drug development process is simple: filing a New Drug
Application with the FDA. Unfortunately this isn't just a single page that says
"please look at our drug!" An NDA can be tens of thousands or perhaps
100,000 or more pages long, and it contains all research and safety data
examined during each of the six prior steps. Still, this stage isn't the point
where the FDA has to make a decision to approve or deny the drug; it's merely
a stepping stone that says it promises to review the application over the next
10 months. If the NDA is accepted a PDUFA, or Prescription Drug User Fee Act,
date is set 10 months down the road (for a standard application) whereby the
FDA is expected to make its decision. Keep in mind the FDA can postpone this
decision or even rule early should it choose.
Step 8: PDUFA date and decision
More often than not, the FDA will wait until the PDUFA date to release its
decision. Essentially the FDA has three choices: it can approve a drug; it can
outright deny a drug (which is pretty rare from what I've witnessed in 15
years), or it can request additional information by sending a complete
response letter, or CRL. A CRL simply states what was lacking that prevented
the drug from being approved and offers suggestions as to how to remedy the
situation. Often times it requires drug developers to run additional studies or
perhaps alter their manufacturing process to appease the FDA. If approved by
the FDA, the drug becomes immediately available for commercial production.
Step 9: Phase 4 clinical studies
"Technically" an approved drug can make it to your medicine cabinet after step
eight, but that doesn't mean the drug developer is off the hook yet. Even after
approval, it's not uncommon for the FDA to request long-term safety studies
be undertaken whereby drug developers are required to submit regular
reports detailing any adverse events with the drug to the FDA. Even following
approval, safety remains the top priority of the FDA.